Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Daniela Matuozzo [verfasserIn] Estelle Talouarn [verfasserIn] Astrid Marchal [verfasserIn] Peng Zhang [verfasserIn] Jeremy Manry [verfasserIn] Yoann Seeleuthner [verfasserIn] Yu Zhang [verfasserIn] Alexandre Bolze [verfasserIn] Matthieu Chaldebas [verfasserIn] Baptiste Milisavljevic [verfasserIn] Adrian Gervais [verfasserIn] Paul Bastard [verfasserIn] Takaki Asano [verfasserIn] Lucy Bizien [verfasserIn] Federica Barzaghi [verfasserIn] Hassan Abolhassani [verfasserIn] Ahmad Abou Tayoun [verfasserIn] Alessandro Aiuti [verfasserIn] Ilad Alavi Darazam [verfasserIn] Luis M. Allende [verfasserIn] Rebeca Alonso-Arias [verfasserIn] Andrés Augusto Arias [verfasserIn] Gokhan Aytekin [verfasserIn] Peter Bergman [verfasserIn] Simone Bondesan [verfasserIn] Yenan T. Bryceson [verfasserIn] Ingrid G. Bustos [verfasserIn] Oscar Cabrera-Marante [verfasserIn] Sheila Carcel [verfasserIn] Paola Carrera [verfasserIn] Giorgio Casari [verfasserIn] Khalil Chaïbi [verfasserIn] Roger Colobran [verfasserIn] Antonio Condino-Neto [verfasserIn] Laura E. Covill [verfasserIn] Ottavia M. Delmonte [verfasserIn] Loubna El Zein [verfasserIn] Carlos Flores [verfasserIn] Peter K. Gregersen [verfasserIn] Marta Gut [verfasserIn] Filomeen Haerynck [verfasserIn] Rabih Halwani [verfasserIn] Selda Hancerli [verfasserIn] Lennart Hammarström [verfasserIn] Nevin Hatipoğlu [verfasserIn] Adem Karbuz [verfasserIn] Sevgi Keles [verfasserIn] Christèle Kyheng [verfasserIn] Rafael Leon-Lopez [verfasserIn] Jose Luis Franco [verfasserIn] Davood Mansouri [verfasserIn] Javier Martinez-Picado [verfasserIn] Ozge Metin Akcan [verfasserIn] Isabelle Migeotte [verfasserIn] Pierre-Emmanuel Morange [verfasserIn] Guillaume Morelle [verfasserIn] Andrea Martin-Nalda [verfasserIn] Giuseppe Novelli [verfasserIn] Antonio Novelli [verfasserIn] Tayfun Ozcelik [verfasserIn] Figen Palabiyik [verfasserIn] Qiang Pan-Hammarström [verfasserIn] Rebeca Pérez de Diego [verfasserIn] Laura Planas-Serra [verfasserIn] Daniel E. Pleguezuelo [verfasserIn] Carolina Prando [verfasserIn] Aurora Pujol [verfasserIn] Luis Felipe Reyes [verfasserIn] Jacques G. Rivière [verfasserIn] Carlos Rodriguez-Gallego [verfasserIn] Julian Rojas [verfasserIn] Patrizia Rovere-Querini [verfasserIn] Agatha Schlüter [verfasserIn] Mohammad Shahrooei [verfasserIn] Ali Sobh [verfasserIn] Pere Soler-Palacin [verfasserIn] Yacine Tandjaoui-Lambiotte [verfasserIn] Imran Tipu [verfasserIn] Cristina Tresoldi [verfasserIn] Jesus Troya [verfasserIn] Diederik van de Beek [verfasserIn] Mayana Zatz [verfasserIn] Pawel Zawadzki [verfasserIn] Saleh Zaid Al-Muhsen [verfasserIn] Mohammed Faraj Alosaimi [verfasserIn] Fahad M. Alsohime [verfasserIn] Hagit Baris-Feldman [verfasserIn] Manish J. Butte [verfasserIn] Stefan N. Constantinescu [verfasserIn] Megan A. Cooper [verfasserIn] Clifton L. Dalgard [verfasserIn] Jacques Fellay [verfasserIn] James R. Heath [verfasserIn] Yu-Lung Lau [verfasserIn] Richard P. Lifton [verfasserIn] Tom Maniatis [verfasserIn] Trine H. Mogensen [verfasserIn] Horst von Bernuth [verfasserIn] Alban Lermine [verfasserIn] Michel Vidaud [verfasserIn] Anne Boland [verfasserIn] Jean-François Deleuze [verfasserIn] Robert Nussbaum [verfasserIn] Amanda Kahn-Kirby [verfasserIn] France Mentre [verfasserIn] Sarah Tubiana [verfasserIn] Guy Gorochov [verfasserIn] Florence Tubach [verfasserIn] Pierre Hausfater [verfasserIn] COVID Human Genetic Effort [verfasserIn] COVIDeF Study Group [verfasserIn] French COVID Cohort Study Group [verfasserIn] CoV-Contact Cohort [verfasserIn] COVID-STORM Clinicians [verfasserIn] COVID Clinicians [verfasserIn] Orchestra Working Group [verfasserIn] Amsterdam UMC Covid-19 Biobank [verfasserIn] NIAID-USUHS COVID Study Group [verfasserIn] Isabelle Meyts [verfasserIn] Shen-Ying Zhang [verfasserIn] Anne Puel [verfasserIn] Luigi D. Notarangelo [verfasserIn] Stephanie Boisson-Dupuis [verfasserIn] Helen C. Su [verfasserIn] Bertrand Boisson [verfasserIn] Emmanuelle Jouanguy [verfasserIn] Jean-Laurent Casanova [verfasserIn] Qian Zhang [verfasserIn] Laurent Abel [verfasserIn] Aurélie Cobat [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Rare variants COVID-19 Immunity Type I interferon

Übergeordnetes Werk:	In: Genome Medicine - BMC, 2016, 15(2023), 1, Seite 25
Übergeordnetes Werk:	volume:15 ; year:2023 ; number:1 ; pages:25

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13073-023-01173-8

Katalog-ID:	DOAJ089021509

Internformat


LEADER	01000naa a22002652 4500
001	DOAJ089021509
003	DE-627
005	20230505020958.0
007	cr uuu---uuuuu
008	230505s2023 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.1186/s13073-023-01173-8 \|2 doi
035			\|a (DE-627)DOAJ089021509
035			\|a (DE-599)DOAJ86e4db2aa39842caa8f2f5c9e6d95290
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
050		0	\|a QH426-470
100	0		\|a Daniela Matuozzo \|e verfasserin \|4 aut
245	1	0	\|a Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
264		1	\|c 2023
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
520			\|a Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
650		4	\|a Rare variants
650		4	\|a COVID-19
650		4	\|a Immunity
650		4	\|a Type I interferon
653		0	\|a Medicine
653		0	\|a R
653		0	\|a Genetics
700	0		\|a Estelle Talouarn \|e verfasserin \|4 aut
700	0		\|a Astrid Marchal \|e verfasserin \|4 aut
700	0		\|a Peng Zhang \|e verfasserin \|4 aut
700	0		\|a Jeremy Manry \|e verfasserin \|4 aut
700	0		\|a Yoann Seeleuthner \|e verfasserin \|4 aut
700	0		\|a Yu Zhang \|e verfasserin \|4 aut
700	0		\|a Alexandre Bolze \|e verfasserin \|4 aut
700	0		\|a Matthieu Chaldebas \|e verfasserin \|4 aut
700	0		\|a Baptiste Milisavljevic \|e verfasserin \|4 aut
700	0		\|a Adrian Gervais \|e verfasserin \|4 aut
700	0		\|a Paul Bastard \|e verfasserin \|4 aut
700	0		\|a Takaki Asano \|e verfasserin \|4 aut
700	0		\|a Lucy Bizien \|e verfasserin \|4 aut
700	0		\|a Federica Barzaghi \|e verfasserin \|4 aut
700	0		\|a Hassan Abolhassani \|e verfasserin \|4 aut
700	0		\|a Ahmad Abou Tayoun \|e verfasserin \|4 aut
700	0		\|a Alessandro Aiuti \|e verfasserin \|4 aut
700	0		\|a Ilad Alavi Darazam \|e verfasserin \|4 aut
700	0		\|a Luis M. Allende \|e verfasserin \|4 aut
700	0		\|a Rebeca Alonso-Arias \|e verfasserin \|4 aut
700	0		\|a Andrés Augusto Arias \|e verfasserin \|4 aut
700	0		\|a Gokhan Aytekin \|e verfasserin \|4 aut
700	0		\|a Peter Bergman \|e verfasserin \|4 aut
700	0		\|a Simone Bondesan \|e verfasserin \|4 aut
700	0		\|a Yenan T. Bryceson \|e verfasserin \|4 aut
700	0		\|a Ingrid G. Bustos \|e verfasserin \|4 aut
700	0		\|a Oscar Cabrera-Marante \|e verfasserin \|4 aut
700	0		\|a Sheila Carcel \|e verfasserin \|4 aut
700	0		\|a Paola Carrera \|e verfasserin \|4 aut
700	0		\|a Giorgio Casari \|e verfasserin \|4 aut
700	0		\|a Khalil Chaïbi \|e verfasserin \|4 aut
700	0		\|a Roger Colobran \|e verfasserin \|4 aut
700	0		\|a Antonio Condino-Neto \|e verfasserin \|4 aut
700	0		\|a Laura E. Covill \|e verfasserin \|4 aut
700	0		\|a Ottavia M. Delmonte \|e verfasserin \|4 aut
700	0		\|a Loubna El Zein \|e verfasserin \|4 aut
700	0		\|a Carlos Flores \|e verfasserin \|4 aut
700	0		\|a Peter K. Gregersen \|e verfasserin \|4 aut
700	0		\|a Marta Gut \|e verfasserin \|4 aut
700	0		\|a Filomeen Haerynck \|e verfasserin \|4 aut
700	0		\|a Rabih Halwani \|e verfasserin \|4 aut
700	0		\|a Selda Hancerli \|e verfasserin \|4 aut
700	0		\|a Lennart Hammarström \|e verfasserin \|4 aut
700	0		\|a Nevin Hatipoğlu \|e verfasserin \|4 aut
700	0		\|a Adem Karbuz \|e verfasserin \|4 aut
700	0		\|a Sevgi Keles \|e verfasserin \|4 aut
700	0		\|a Christèle Kyheng \|e verfasserin \|4 aut
700	0		\|a Rafael Leon-Lopez \|e verfasserin \|4 aut
700	0		\|a Jose Luis Franco \|e verfasserin \|4 aut
700	0		\|a Davood Mansouri \|e verfasserin \|4 aut
700	0		\|a Javier Martinez-Picado \|e verfasserin \|4 aut
700	0		\|a Ozge Metin Akcan \|e verfasserin \|4 aut
700	0		\|a Isabelle Migeotte \|e verfasserin \|4 aut
700	0		\|a Pierre-Emmanuel Morange \|e verfasserin \|4 aut
700	0		\|a Guillaume Morelle \|e verfasserin \|4 aut
700	0		\|a Andrea Martin-Nalda \|e verfasserin \|4 aut
700	0		\|a Giuseppe Novelli \|e verfasserin \|4 aut
700	0		\|a Antonio Novelli \|e verfasserin \|4 aut
700	0		\|a Tayfun Ozcelik \|e verfasserin \|4 aut
700	0		\|a Figen Palabiyik \|e verfasserin \|4 aut
700	0		\|a Qiang Pan-Hammarström \|e verfasserin \|4 aut
700	0		\|a Rebeca Pérez de Diego \|e verfasserin \|4 aut
700	0		\|a Laura Planas-Serra \|e verfasserin \|4 aut
700	0		\|a Daniel E. Pleguezuelo \|e verfasserin \|4 aut
700	0		\|a Carolina Prando \|e verfasserin \|4 aut
700	0		\|a Aurora Pujol \|e verfasserin \|4 aut
700	0		\|a Luis Felipe Reyes \|e verfasserin \|4 aut
700	0		\|a Jacques G. Rivière \|e verfasserin \|4 aut
700	0		\|a Carlos Rodriguez-Gallego \|e verfasserin \|4 aut
700	0		\|a Julian Rojas \|e verfasserin \|4 aut
700	0		\|a Patrizia Rovere-Querini \|e verfasserin \|4 aut
700	0		\|a Agatha Schlüter \|e verfasserin \|4 aut
700	0		\|a Mohammad Shahrooei \|e verfasserin \|4 aut
700	0		\|a Ali Sobh \|e verfasserin \|4 aut
700	0		\|a Pere Soler-Palacin \|e verfasserin \|4 aut
700	0		\|a Yacine Tandjaoui-Lambiotte \|e verfasserin \|4 aut
700	0		\|a Imran Tipu \|e verfasserin \|4 aut
700	0		\|a Cristina Tresoldi \|e verfasserin \|4 aut
700	0		\|a Jesus Troya \|e verfasserin \|4 aut
700	0		\|a Diederik van de Beek \|e verfasserin \|4 aut
700	0		\|a Mayana Zatz \|e verfasserin \|4 aut
700	0		\|a Pawel Zawadzki \|e verfasserin \|4 aut
700	0		\|a Saleh Zaid Al-Muhsen \|e verfasserin \|4 aut
700	0		\|a Mohammed Faraj Alosaimi \|e verfasserin \|4 aut
700	0		\|a Fahad M. Alsohime \|e verfasserin \|4 aut
700	0		\|a Hagit Baris-Feldman \|e verfasserin \|4 aut
700	0		\|a Manish J. Butte \|e verfasserin \|4 aut
700	0		\|a Stefan N. Constantinescu \|e verfasserin \|4 aut
700	0		\|a Megan A. Cooper \|e verfasserin \|4 aut
700	0		\|a Clifton L. Dalgard \|e verfasserin \|4 aut
700	0		\|a Jacques Fellay \|e verfasserin \|4 aut
700	0		\|a James R. Heath \|e verfasserin \|4 aut
700	0		\|a Yu-Lung Lau \|e verfasserin \|4 aut
700	0		\|a Richard P. Lifton \|e verfasserin \|4 aut
700	0		\|a Tom Maniatis \|e verfasserin \|4 aut
700	0		\|a Trine H. Mogensen \|e verfasserin \|4 aut
700	0		\|a Horst von Bernuth \|e verfasserin \|4 aut
700	0		\|a Alban Lermine \|e verfasserin \|4 aut
700	0		\|a Michel Vidaud \|e verfasserin \|4 aut
700	0		\|a Anne Boland \|e verfasserin \|4 aut
700	0		\|a Jean-François Deleuze \|e verfasserin \|4 aut
700	0		\|a Robert Nussbaum \|e verfasserin \|4 aut
700	0		\|a Amanda Kahn-Kirby \|e verfasserin \|4 aut
700	0		\|a France Mentre \|e verfasserin \|4 aut
700	0		\|a Sarah Tubiana \|e verfasserin \|4 aut
700	0		\|a Guy Gorochov \|e verfasserin \|4 aut
700	0		\|a Florence Tubach \|e verfasserin \|4 aut
700	0		\|a Pierre Hausfater \|e verfasserin \|4 aut
700	0		\|a COVID Human Genetic Effort \|e verfasserin \|4 aut
700	0		\|a COVIDeF Study Group \|e verfasserin \|4 aut
700	0		\|a French COVID Cohort Study Group \|e verfasserin \|4 aut
700	0		\|a CoV-Contact Cohort \|e verfasserin \|4 aut
700	0		\|a COVID-STORM Clinicians \|e verfasserin \|4 aut
700	0		\|a COVID Clinicians \|e verfasserin \|4 aut
700	0		\|a Orchestra Working Group \|e verfasserin \|4 aut
700	0		\|a Amsterdam UMC Covid-19 Biobank \|e verfasserin \|4 aut
700	0		\|a NIAID-USUHS COVID Study Group \|e verfasserin \|4 aut
700	0		\|a Isabelle Meyts \|e verfasserin \|4 aut
700	0		\|a Shen-Ying Zhang \|e verfasserin \|4 aut
700	0		\|a Anne Puel \|e verfasserin \|4 aut
700	0		\|a Luigi D. Notarangelo \|e verfasserin \|4 aut
700	0		\|a Stephanie Boisson-Dupuis \|e verfasserin \|4 aut
700	0		\|a Helen C. Su \|e verfasserin \|4 aut
700	0		\|a Bertrand Boisson \|e verfasserin \|4 aut
700	0		\|a Emmanuelle Jouanguy \|e verfasserin \|4 aut
700	0		\|a Jean-Laurent Casanova \|e verfasserin \|4 aut
700	0		\|a Qian Zhang \|e verfasserin \|4 aut
700	0		\|a Laurent Abel \|e verfasserin \|4 aut
700	0		\|a Aurélie Cobat \|e verfasserin \|4 aut
773	0	8	\|i In \|t Genome Medicine \|d BMC, 2016 \|g 15(2023), 1, Seite 25 \|w (DE-627)594424275 \|w (DE-600)2484394-5 \|x 1756994X \|7 nnns
773	1	8	\|g volume:15 \|g year:2023 \|g number:1 \|g pages:25
856	4	0	\|u https://doi.org/10.1186/s13073-023-01173-8 \|z kostenfrei
856	4	0	\|u https://doaj.org/article/86e4db2aa39842caa8f2f5c9e6d95290 \|z kostenfrei
856	4	0	\|u https://doi.org/10.1186/s13073-023-01173-8 \|z kostenfrei
856	4	2	\|u https://doaj.org/toc/1756-994X \|y Journal toc \|z kostenfrei
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_DOAJ
912			\|a GBV_ILN_11
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_230
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_602
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 15 \|j 2023 \|e 1 \|h 25

Indexfelder

matchkey_str	article:1756994X:2023----::aerdcelsofntovratotpifimntgnsrascaew
hierarchy_sort_str	2023
callnumber-subject-code	QH
publishDate	2023
allfields	10.1186/s13073-023-01173-8 doi (DE-627)DOAJ089021509 (DE-599)DOAJ86e4db2aa39842caa8f2f5c9e6d95290 DE-627 ger DE-627 rakwb eng QH426-470 Daniela Matuozzo verfasserin aut Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. Rare variants COVID-19 Immunity Type I interferon Medicine R Genetics Estelle Talouarn verfasserin aut Astrid Marchal verfasserin aut Peng Zhang verfasserin aut Jeremy Manry verfasserin aut Yoann Seeleuthner verfasserin aut Yu Zhang verfasserin aut Alexandre Bolze verfasserin aut Matthieu Chaldebas verfasserin aut Baptiste Milisavljevic verfasserin aut Adrian Gervais verfasserin aut Paul Bastard verfasserin aut Takaki Asano verfasserin aut Lucy Bizien verfasserin aut Federica Barzaghi verfasserin aut Hassan Abolhassani verfasserin aut Ahmad Abou Tayoun verfasserin aut Alessandro Aiuti verfasserin aut Ilad Alavi Darazam verfasserin aut Luis M. Allende verfasserin aut Rebeca Alonso-Arias verfasserin aut Andrés Augusto Arias verfasserin aut Gokhan Aytekin verfasserin aut Peter Bergman verfasserin aut Simone Bondesan verfasserin aut Yenan T. Bryceson verfasserin aut Ingrid G. Bustos verfasserin aut Oscar Cabrera-Marante verfasserin aut Sheila Carcel verfasserin aut Paola Carrera verfasserin aut Giorgio Casari verfasserin aut Khalil Chaïbi verfasserin aut Roger Colobran verfasserin aut Antonio Condino-Neto verfasserin aut Laura E. Covill verfasserin aut Ottavia M. Delmonte verfasserin aut Loubna El Zein verfasserin aut Carlos Flores verfasserin aut Peter K. Gregersen verfasserin aut Marta Gut verfasserin aut Filomeen Haerynck verfasserin aut Rabih Halwani verfasserin aut Selda Hancerli verfasserin aut Lennart Hammarström verfasserin aut Nevin Hatipoğlu verfasserin aut Adem Karbuz verfasserin aut Sevgi Keles verfasserin aut Christèle Kyheng verfasserin aut Rafael Leon-Lopez verfasserin aut Jose Luis Franco verfasserin aut Davood Mansouri verfasserin aut Javier Martinez-Picado verfasserin aut Ozge Metin Akcan verfasserin aut Isabelle Migeotte verfasserin aut Pierre-Emmanuel Morange verfasserin aut Guillaume Morelle verfasserin aut Andrea Martin-Nalda verfasserin aut Giuseppe Novelli verfasserin aut Antonio Novelli verfasserin aut Tayfun Ozcelik verfasserin aut Figen Palabiyik verfasserin aut Qiang Pan-Hammarström verfasserin aut Rebeca Pérez de Diego verfasserin aut Laura Planas-Serra verfasserin aut Daniel E. Pleguezuelo verfasserin aut Carolina Prando verfasserin aut Aurora Pujol verfasserin aut Luis Felipe Reyes verfasserin aut Jacques G. Rivière verfasserin aut Carlos Rodriguez-Gallego verfasserin aut Julian Rojas verfasserin aut Patrizia Rovere-Querini verfasserin aut Agatha Schlüter verfasserin aut Mohammad Shahrooei verfasserin aut Ali Sobh verfasserin aut Pere Soler-Palacin verfasserin aut Yacine Tandjaoui-Lambiotte verfasserin aut Imran Tipu verfasserin aut Cristina Tresoldi verfasserin aut Jesus Troya verfasserin aut Diederik van de Beek verfasserin aut Mayana Zatz verfasserin aut Pawel Zawadzki verfasserin aut Saleh Zaid Al-Muhsen verfasserin aut Mohammed Faraj Alosaimi verfasserin aut Fahad M. Alsohime verfasserin aut Hagit Baris-Feldman verfasserin aut Manish J. Butte verfasserin aut Stefan N. Constantinescu verfasserin aut Megan A. Cooper verfasserin aut Clifton L. Dalgard verfasserin aut Jacques Fellay verfasserin aut James R. Heath verfasserin aut Yu-Lung Lau verfasserin aut Richard P. Lifton verfasserin aut Tom Maniatis verfasserin aut Trine H. Mogensen verfasserin aut Horst von Bernuth verfasserin aut Alban Lermine verfasserin aut Michel Vidaud verfasserin aut Anne Boland verfasserin aut Jean-François Deleuze verfasserin aut Robert Nussbaum verfasserin aut Amanda Kahn-Kirby verfasserin aut France Mentre verfasserin aut Sarah Tubiana verfasserin aut Guy Gorochov verfasserin aut Florence Tubach verfasserin aut Pierre Hausfater verfasserin aut COVID Human Genetic Effort verfasserin aut COVIDeF Study Group verfasserin aut French COVID Cohort Study Group verfasserin aut CoV-Contact Cohort verfasserin aut COVID-STORM Clinicians verfasserin aut COVID Clinicians verfasserin aut Orchestra Working Group verfasserin aut Amsterdam UMC Covid-19 Biobank verfasserin aut NIAID-USUHS COVID Study Group verfasserin aut Isabelle Meyts verfasserin aut Shen-Ying Zhang verfasserin aut Anne Puel verfasserin aut Luigi D. Notarangelo verfasserin aut Stephanie Boisson-Dupuis verfasserin aut Helen C. Su verfasserin aut Bertrand Boisson verfasserin aut Emmanuelle Jouanguy verfasserin aut Jean-Laurent Casanova verfasserin aut Qian Zhang verfasserin aut Laurent Abel verfasserin aut Aurélie Cobat verfasserin aut In Genome Medicine BMC, 2016 15(2023), 1, Seite 25 (DE-627)594424275 (DE-600)2484394-5 1756994X nnns volume:15 year:2023 number:1 pages:25 https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/article/86e4db2aa39842caa8f2f5c9e6d95290 kostenfrei https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/toc/1756-994X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 25
spelling	10.1186/s13073-023-01173-8 doi (DE-627)DOAJ089021509 (DE-599)DOAJ86e4db2aa39842caa8f2f5c9e6d95290 DE-627 ger DE-627 rakwb eng QH426-470 Daniela Matuozzo verfasserin aut Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. Rare variants COVID-19 Immunity Type I interferon Medicine R Genetics Estelle Talouarn verfasserin aut Astrid Marchal verfasserin aut Peng Zhang verfasserin aut Jeremy Manry verfasserin aut Yoann Seeleuthner verfasserin aut Yu Zhang verfasserin aut Alexandre Bolze verfasserin aut Matthieu Chaldebas verfasserin aut Baptiste Milisavljevic verfasserin aut Adrian Gervais verfasserin aut Paul Bastard verfasserin aut Takaki Asano verfasserin aut Lucy Bizien verfasserin aut Federica Barzaghi verfasserin aut Hassan Abolhassani verfasserin aut Ahmad Abou Tayoun verfasserin aut Alessandro Aiuti verfasserin aut Ilad Alavi Darazam verfasserin aut Luis M. Allende verfasserin aut Rebeca Alonso-Arias verfasserin aut Andrés Augusto Arias verfasserin aut Gokhan Aytekin verfasserin aut Peter Bergman verfasserin aut Simone Bondesan verfasserin aut Yenan T. Bryceson verfasserin aut Ingrid G. Bustos verfasserin aut Oscar Cabrera-Marante verfasserin aut Sheila Carcel verfasserin aut Paola Carrera verfasserin aut Giorgio Casari verfasserin aut Khalil Chaïbi verfasserin aut Roger Colobran verfasserin aut Antonio Condino-Neto verfasserin aut Laura E. Covill verfasserin aut Ottavia M. Delmonte verfasserin aut Loubna El Zein verfasserin aut Carlos Flores verfasserin aut Peter K. Gregersen verfasserin aut Marta Gut verfasserin aut Filomeen Haerynck verfasserin aut Rabih Halwani verfasserin aut Selda Hancerli verfasserin aut Lennart Hammarström verfasserin aut Nevin Hatipoğlu verfasserin aut Adem Karbuz verfasserin aut Sevgi Keles verfasserin aut Christèle Kyheng verfasserin aut Rafael Leon-Lopez verfasserin aut Jose Luis Franco verfasserin aut Davood Mansouri verfasserin aut Javier Martinez-Picado verfasserin aut Ozge Metin Akcan verfasserin aut Isabelle Migeotte verfasserin aut Pierre-Emmanuel Morange verfasserin aut Guillaume Morelle verfasserin aut Andrea Martin-Nalda verfasserin aut Giuseppe Novelli verfasserin aut Antonio Novelli verfasserin aut Tayfun Ozcelik verfasserin aut Figen Palabiyik verfasserin aut Qiang Pan-Hammarström verfasserin aut Rebeca Pérez de Diego verfasserin aut Laura Planas-Serra verfasserin aut Daniel E. Pleguezuelo verfasserin aut Carolina Prando verfasserin aut Aurora Pujol verfasserin aut Luis Felipe Reyes verfasserin aut Jacques G. Rivière verfasserin aut Carlos Rodriguez-Gallego verfasserin aut Julian Rojas verfasserin aut Patrizia Rovere-Querini verfasserin aut Agatha Schlüter verfasserin aut Mohammad Shahrooei verfasserin aut Ali Sobh verfasserin aut Pere Soler-Palacin verfasserin aut Yacine Tandjaoui-Lambiotte verfasserin aut Imran Tipu verfasserin aut Cristina Tresoldi verfasserin aut Jesus Troya verfasserin aut Diederik van de Beek verfasserin aut Mayana Zatz verfasserin aut Pawel Zawadzki verfasserin aut Saleh Zaid Al-Muhsen verfasserin aut Mohammed Faraj Alosaimi verfasserin aut Fahad M. Alsohime verfasserin aut Hagit Baris-Feldman verfasserin aut Manish J. Butte verfasserin aut Stefan N. Constantinescu verfasserin aut Megan A. Cooper verfasserin aut Clifton L. Dalgard verfasserin aut Jacques Fellay verfasserin aut James R. Heath verfasserin aut Yu-Lung Lau verfasserin aut Richard P. Lifton verfasserin aut Tom Maniatis verfasserin aut Trine H. Mogensen verfasserin aut Horst von Bernuth verfasserin aut Alban Lermine verfasserin aut Michel Vidaud verfasserin aut Anne Boland verfasserin aut Jean-François Deleuze verfasserin aut Robert Nussbaum verfasserin aut Amanda Kahn-Kirby verfasserin aut France Mentre verfasserin aut Sarah Tubiana verfasserin aut Guy Gorochov verfasserin aut Florence Tubach verfasserin aut Pierre Hausfater verfasserin aut COVID Human Genetic Effort verfasserin aut COVIDeF Study Group verfasserin aut French COVID Cohort Study Group verfasserin aut CoV-Contact Cohort verfasserin aut COVID-STORM Clinicians verfasserin aut COVID Clinicians verfasserin aut Orchestra Working Group verfasserin aut Amsterdam UMC Covid-19 Biobank verfasserin aut NIAID-USUHS COVID Study Group verfasserin aut Isabelle Meyts verfasserin aut Shen-Ying Zhang verfasserin aut Anne Puel verfasserin aut Luigi D. Notarangelo verfasserin aut Stephanie Boisson-Dupuis verfasserin aut Helen C. Su verfasserin aut Bertrand Boisson verfasserin aut Emmanuelle Jouanguy verfasserin aut Jean-Laurent Casanova verfasserin aut Qian Zhang verfasserin aut Laurent Abel verfasserin aut Aurélie Cobat verfasserin aut In Genome Medicine BMC, 2016 15(2023), 1, Seite 25 (DE-627)594424275 (DE-600)2484394-5 1756994X nnns volume:15 year:2023 number:1 pages:25 https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/article/86e4db2aa39842caa8f2f5c9e6d95290 kostenfrei https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/toc/1756-994X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 25
allfields_unstemmed	10.1186/s13073-023-01173-8 doi (DE-627)DOAJ089021509 (DE-599)DOAJ86e4db2aa39842caa8f2f5c9e6d95290 DE-627 ger DE-627 rakwb eng QH426-470 Daniela Matuozzo verfasserin aut Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. Rare variants COVID-19 Immunity Type I interferon Medicine R Genetics Estelle Talouarn verfasserin aut Astrid Marchal verfasserin aut Peng Zhang verfasserin aut Jeremy Manry verfasserin aut Yoann Seeleuthner verfasserin aut Yu Zhang verfasserin aut Alexandre Bolze verfasserin aut Matthieu Chaldebas verfasserin aut Baptiste Milisavljevic verfasserin aut Adrian Gervais verfasserin aut Paul Bastard verfasserin aut Takaki Asano verfasserin aut Lucy Bizien verfasserin aut Federica Barzaghi verfasserin aut Hassan Abolhassani verfasserin aut Ahmad Abou Tayoun verfasserin aut Alessandro Aiuti verfasserin aut Ilad Alavi Darazam verfasserin aut Luis M. Allende verfasserin aut Rebeca Alonso-Arias verfasserin aut Andrés Augusto Arias verfasserin aut Gokhan Aytekin verfasserin aut Peter Bergman verfasserin aut Simone Bondesan verfasserin aut Yenan T. Bryceson verfasserin aut Ingrid G. Bustos verfasserin aut Oscar Cabrera-Marante verfasserin aut Sheila Carcel verfasserin aut Paola Carrera verfasserin aut Giorgio Casari verfasserin aut Khalil Chaïbi verfasserin aut Roger Colobran verfasserin aut Antonio Condino-Neto verfasserin aut Laura E. Covill verfasserin aut Ottavia M. Delmonte verfasserin aut Loubna El Zein verfasserin aut Carlos Flores verfasserin aut Peter K. Gregersen verfasserin aut Marta Gut verfasserin aut Filomeen Haerynck verfasserin aut Rabih Halwani verfasserin aut Selda Hancerli verfasserin aut Lennart Hammarström verfasserin aut Nevin Hatipoğlu verfasserin aut Adem Karbuz verfasserin aut Sevgi Keles verfasserin aut Christèle Kyheng verfasserin aut Rafael Leon-Lopez verfasserin aut Jose Luis Franco verfasserin aut Davood Mansouri verfasserin aut Javier Martinez-Picado verfasserin aut Ozge Metin Akcan verfasserin aut Isabelle Migeotte verfasserin aut Pierre-Emmanuel Morange verfasserin aut Guillaume Morelle verfasserin aut Andrea Martin-Nalda verfasserin aut Giuseppe Novelli verfasserin aut Antonio Novelli verfasserin aut Tayfun Ozcelik verfasserin aut Figen Palabiyik verfasserin aut Qiang Pan-Hammarström verfasserin aut Rebeca Pérez de Diego verfasserin aut Laura Planas-Serra verfasserin aut Daniel E. Pleguezuelo verfasserin aut Carolina Prando verfasserin aut Aurora Pujol verfasserin aut Luis Felipe Reyes verfasserin aut Jacques G. Rivière verfasserin aut Carlos Rodriguez-Gallego verfasserin aut Julian Rojas verfasserin aut Patrizia Rovere-Querini verfasserin aut Agatha Schlüter verfasserin aut Mohammad Shahrooei verfasserin aut Ali Sobh verfasserin aut Pere Soler-Palacin verfasserin aut Yacine Tandjaoui-Lambiotte verfasserin aut Imran Tipu verfasserin aut Cristina Tresoldi verfasserin aut Jesus Troya verfasserin aut Diederik van de Beek verfasserin aut Mayana Zatz verfasserin aut Pawel Zawadzki verfasserin aut Saleh Zaid Al-Muhsen verfasserin aut Mohammed Faraj Alosaimi verfasserin aut Fahad M. Alsohime verfasserin aut Hagit Baris-Feldman verfasserin aut Manish J. Butte verfasserin aut Stefan N. Constantinescu verfasserin aut Megan A. Cooper verfasserin aut Clifton L. Dalgard verfasserin aut Jacques Fellay verfasserin aut James R. Heath verfasserin aut Yu-Lung Lau verfasserin aut Richard P. Lifton verfasserin aut Tom Maniatis verfasserin aut Trine H. Mogensen verfasserin aut Horst von Bernuth verfasserin aut Alban Lermine verfasserin aut Michel Vidaud verfasserin aut Anne Boland verfasserin aut Jean-François Deleuze verfasserin aut Robert Nussbaum verfasserin aut Amanda Kahn-Kirby verfasserin aut France Mentre verfasserin aut Sarah Tubiana verfasserin aut Guy Gorochov verfasserin aut Florence Tubach verfasserin aut Pierre Hausfater verfasserin aut COVID Human Genetic Effort verfasserin aut COVIDeF Study Group verfasserin aut French COVID Cohort Study Group verfasserin aut CoV-Contact Cohort verfasserin aut COVID-STORM Clinicians verfasserin aut COVID Clinicians verfasserin aut Orchestra Working Group verfasserin aut Amsterdam UMC Covid-19 Biobank verfasserin aut NIAID-USUHS COVID Study Group verfasserin aut Isabelle Meyts verfasserin aut Shen-Ying Zhang verfasserin aut Anne Puel verfasserin aut Luigi D. Notarangelo verfasserin aut Stephanie Boisson-Dupuis verfasserin aut Helen C. Su verfasserin aut Bertrand Boisson verfasserin aut Emmanuelle Jouanguy verfasserin aut Jean-Laurent Casanova verfasserin aut Qian Zhang verfasserin aut Laurent Abel verfasserin aut Aurélie Cobat verfasserin aut In Genome Medicine BMC, 2016 15(2023), 1, Seite 25 (DE-627)594424275 (DE-600)2484394-5 1756994X nnns volume:15 year:2023 number:1 pages:25 https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/article/86e4db2aa39842caa8f2f5c9e6d95290 kostenfrei https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/toc/1756-994X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 25
allfieldsGer	10.1186/s13073-023-01173-8 doi (DE-627)DOAJ089021509 (DE-599)DOAJ86e4db2aa39842caa8f2f5c9e6d95290 DE-627 ger DE-627 rakwb eng QH426-470 Daniela Matuozzo verfasserin aut Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. Rare variants COVID-19 Immunity Type I interferon Medicine R Genetics Estelle Talouarn verfasserin aut Astrid Marchal verfasserin aut Peng Zhang verfasserin aut Jeremy Manry verfasserin aut Yoann Seeleuthner verfasserin aut Yu Zhang verfasserin aut Alexandre Bolze verfasserin aut Matthieu Chaldebas verfasserin aut Baptiste Milisavljevic verfasserin aut Adrian Gervais verfasserin aut Paul Bastard verfasserin aut Takaki Asano verfasserin aut Lucy Bizien verfasserin aut Federica Barzaghi verfasserin aut Hassan Abolhassani verfasserin aut Ahmad Abou Tayoun verfasserin aut Alessandro Aiuti verfasserin aut Ilad Alavi Darazam verfasserin aut Luis M. Allende verfasserin aut Rebeca Alonso-Arias verfasserin aut Andrés Augusto Arias verfasserin aut Gokhan Aytekin verfasserin aut Peter Bergman verfasserin aut Simone Bondesan verfasserin aut Yenan T. Bryceson verfasserin aut Ingrid G. Bustos verfasserin aut Oscar Cabrera-Marante verfasserin aut Sheila Carcel verfasserin aut Paola Carrera verfasserin aut Giorgio Casari verfasserin aut Khalil Chaïbi verfasserin aut Roger Colobran verfasserin aut Antonio Condino-Neto verfasserin aut Laura E. Covill verfasserin aut Ottavia M. Delmonte verfasserin aut Loubna El Zein verfasserin aut Carlos Flores verfasserin aut Peter K. Gregersen verfasserin aut Marta Gut verfasserin aut Filomeen Haerynck verfasserin aut Rabih Halwani verfasserin aut Selda Hancerli verfasserin aut Lennart Hammarström verfasserin aut Nevin Hatipoğlu verfasserin aut Adem Karbuz verfasserin aut Sevgi Keles verfasserin aut Christèle Kyheng verfasserin aut Rafael Leon-Lopez verfasserin aut Jose Luis Franco verfasserin aut Davood Mansouri verfasserin aut Javier Martinez-Picado verfasserin aut Ozge Metin Akcan verfasserin aut Isabelle Migeotte verfasserin aut Pierre-Emmanuel Morange verfasserin aut Guillaume Morelle verfasserin aut Andrea Martin-Nalda verfasserin aut Giuseppe Novelli verfasserin aut Antonio Novelli verfasserin aut Tayfun Ozcelik verfasserin aut Figen Palabiyik verfasserin aut Qiang Pan-Hammarström verfasserin aut Rebeca Pérez de Diego verfasserin aut Laura Planas-Serra verfasserin aut Daniel E. Pleguezuelo verfasserin aut Carolina Prando verfasserin aut Aurora Pujol verfasserin aut Luis Felipe Reyes verfasserin aut Jacques G. Rivière verfasserin aut Carlos Rodriguez-Gallego verfasserin aut Julian Rojas verfasserin aut Patrizia Rovere-Querini verfasserin aut Agatha Schlüter verfasserin aut Mohammad Shahrooei verfasserin aut Ali Sobh verfasserin aut Pere Soler-Palacin verfasserin aut Yacine Tandjaoui-Lambiotte verfasserin aut Imran Tipu verfasserin aut Cristina Tresoldi verfasserin aut Jesus Troya verfasserin aut Diederik van de Beek verfasserin aut Mayana Zatz verfasserin aut Pawel Zawadzki verfasserin aut Saleh Zaid Al-Muhsen verfasserin aut Mohammed Faraj Alosaimi verfasserin aut Fahad M. Alsohime verfasserin aut Hagit Baris-Feldman verfasserin aut Manish J. Butte verfasserin aut Stefan N. Constantinescu verfasserin aut Megan A. Cooper verfasserin aut Clifton L. Dalgard verfasserin aut Jacques Fellay verfasserin aut James R. Heath verfasserin aut Yu-Lung Lau verfasserin aut Richard P. Lifton verfasserin aut Tom Maniatis verfasserin aut Trine H. Mogensen verfasserin aut Horst von Bernuth verfasserin aut Alban Lermine verfasserin aut Michel Vidaud verfasserin aut Anne Boland verfasserin aut Jean-François Deleuze verfasserin aut Robert Nussbaum verfasserin aut Amanda Kahn-Kirby verfasserin aut France Mentre verfasserin aut Sarah Tubiana verfasserin aut Guy Gorochov verfasserin aut Florence Tubach verfasserin aut Pierre Hausfater verfasserin aut COVID Human Genetic Effort verfasserin aut COVIDeF Study Group verfasserin aut French COVID Cohort Study Group verfasserin aut CoV-Contact Cohort verfasserin aut COVID-STORM Clinicians verfasserin aut COVID Clinicians verfasserin aut Orchestra Working Group verfasserin aut Amsterdam UMC Covid-19 Biobank verfasserin aut NIAID-USUHS COVID Study Group verfasserin aut Isabelle Meyts verfasserin aut Shen-Ying Zhang verfasserin aut Anne Puel verfasserin aut Luigi D. Notarangelo verfasserin aut Stephanie Boisson-Dupuis verfasserin aut Helen C. Su verfasserin aut Bertrand Boisson verfasserin aut Emmanuelle Jouanguy verfasserin aut Jean-Laurent Casanova verfasserin aut Qian Zhang verfasserin aut Laurent Abel verfasserin aut Aurélie Cobat verfasserin aut In Genome Medicine BMC, 2016 15(2023), 1, Seite 25 (DE-627)594424275 (DE-600)2484394-5 1756994X nnns volume:15 year:2023 number:1 pages:25 https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/article/86e4db2aa39842caa8f2f5c9e6d95290 kostenfrei https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/toc/1756-994X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 25
allfieldsSound	10.1186/s13073-023-01173-8 doi (DE-627)DOAJ089021509 (DE-599)DOAJ86e4db2aa39842caa8f2f5c9e6d95290 DE-627 ger DE-627 rakwb eng QH426-470 Daniela Matuozzo verfasserin aut Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. Rare variants COVID-19 Immunity Type I interferon Medicine R Genetics Estelle Talouarn verfasserin aut Astrid Marchal verfasserin aut Peng Zhang verfasserin aut Jeremy Manry verfasserin aut Yoann Seeleuthner verfasserin aut Yu Zhang verfasserin aut Alexandre Bolze verfasserin aut Matthieu Chaldebas verfasserin aut Baptiste Milisavljevic verfasserin aut Adrian Gervais verfasserin aut Paul Bastard verfasserin aut Takaki Asano verfasserin aut Lucy Bizien verfasserin aut Federica Barzaghi verfasserin aut Hassan Abolhassani verfasserin aut Ahmad Abou Tayoun verfasserin aut Alessandro Aiuti verfasserin aut Ilad Alavi Darazam verfasserin aut Luis M. Allende verfasserin aut Rebeca Alonso-Arias verfasserin aut Andrés Augusto Arias verfasserin aut Gokhan Aytekin verfasserin aut Peter Bergman verfasserin aut Simone Bondesan verfasserin aut Yenan T. Bryceson verfasserin aut Ingrid G. Bustos verfasserin aut Oscar Cabrera-Marante verfasserin aut Sheila Carcel verfasserin aut Paola Carrera verfasserin aut Giorgio Casari verfasserin aut Khalil Chaïbi verfasserin aut Roger Colobran verfasserin aut Antonio Condino-Neto verfasserin aut Laura E. Covill verfasserin aut Ottavia M. Delmonte verfasserin aut Loubna El Zein verfasserin aut Carlos Flores verfasserin aut Peter K. Gregersen verfasserin aut Marta Gut verfasserin aut Filomeen Haerynck verfasserin aut Rabih Halwani verfasserin aut Selda Hancerli verfasserin aut Lennart Hammarström verfasserin aut Nevin Hatipoğlu verfasserin aut Adem Karbuz verfasserin aut Sevgi Keles verfasserin aut Christèle Kyheng verfasserin aut Rafael Leon-Lopez verfasserin aut Jose Luis Franco verfasserin aut Davood Mansouri verfasserin aut Javier Martinez-Picado verfasserin aut Ozge Metin Akcan verfasserin aut Isabelle Migeotte verfasserin aut Pierre-Emmanuel Morange verfasserin aut Guillaume Morelle verfasserin aut Andrea Martin-Nalda verfasserin aut Giuseppe Novelli verfasserin aut Antonio Novelli verfasserin aut Tayfun Ozcelik verfasserin aut Figen Palabiyik verfasserin aut Qiang Pan-Hammarström verfasserin aut Rebeca Pérez de Diego verfasserin aut Laura Planas-Serra verfasserin aut Daniel E. Pleguezuelo verfasserin aut Carolina Prando verfasserin aut Aurora Pujol verfasserin aut Luis Felipe Reyes verfasserin aut Jacques G. Rivière verfasserin aut Carlos Rodriguez-Gallego verfasserin aut Julian Rojas verfasserin aut Patrizia Rovere-Querini verfasserin aut Agatha Schlüter verfasserin aut Mohammad Shahrooei verfasserin aut Ali Sobh verfasserin aut Pere Soler-Palacin verfasserin aut Yacine Tandjaoui-Lambiotte verfasserin aut Imran Tipu verfasserin aut Cristina Tresoldi verfasserin aut Jesus Troya verfasserin aut Diederik van de Beek verfasserin aut Mayana Zatz verfasserin aut Pawel Zawadzki verfasserin aut Saleh Zaid Al-Muhsen verfasserin aut Mohammed Faraj Alosaimi verfasserin aut Fahad M. Alsohime verfasserin aut Hagit Baris-Feldman verfasserin aut Manish J. Butte verfasserin aut Stefan N. Constantinescu verfasserin aut Megan A. Cooper verfasserin aut Clifton L. Dalgard verfasserin aut Jacques Fellay verfasserin aut James R. Heath verfasserin aut Yu-Lung Lau verfasserin aut Richard P. Lifton verfasserin aut Tom Maniatis verfasserin aut Trine H. Mogensen verfasserin aut Horst von Bernuth verfasserin aut Alban Lermine verfasserin aut Michel Vidaud verfasserin aut Anne Boland verfasserin aut Jean-François Deleuze verfasserin aut Robert Nussbaum verfasserin aut Amanda Kahn-Kirby verfasserin aut France Mentre verfasserin aut Sarah Tubiana verfasserin aut Guy Gorochov verfasserin aut Florence Tubach verfasserin aut Pierre Hausfater verfasserin aut COVID Human Genetic Effort verfasserin aut COVIDeF Study Group verfasserin aut French COVID Cohort Study Group verfasserin aut CoV-Contact Cohort verfasserin aut COVID-STORM Clinicians verfasserin aut COVID Clinicians verfasserin aut Orchestra Working Group verfasserin aut Amsterdam UMC Covid-19 Biobank verfasserin aut NIAID-USUHS COVID Study Group verfasserin aut Isabelle Meyts verfasserin aut Shen-Ying Zhang verfasserin aut Anne Puel verfasserin aut Luigi D. Notarangelo verfasserin aut Stephanie Boisson-Dupuis verfasserin aut Helen C. Su verfasserin aut Bertrand Boisson verfasserin aut Emmanuelle Jouanguy verfasserin aut Jean-Laurent Casanova verfasserin aut Qian Zhang verfasserin aut Laurent Abel verfasserin aut Aurélie Cobat verfasserin aut In Genome Medicine BMC, 2016 15(2023), 1, Seite 25 (DE-627)594424275 (DE-600)2484394-5 1756994X nnns volume:15 year:2023 number:1 pages:25 https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/article/86e4db2aa39842caa8f2f5c9e6d95290 kostenfrei https://doi.org/10.1186/s13073-023-01173-8 kostenfrei https://doaj.org/toc/1756-994X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2023 1 25
language	English
source	In Genome Medicine 15(2023), 1, Seite 25 volume:15 year:2023 number:1 pages:25
sourceStr	In Genome Medicine 15(2023), 1, Seite 25 volume:15 year:2023 number:1 pages:25
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Rare variants COVID-19 Immunity Type I interferon Medicine R Genetics
isfreeaccess_bool	true
container_title	Genome Medicine
authorswithroles_txt_mv	Daniela Matuozzo @@aut@@ Estelle Talouarn @@aut@@ Astrid Marchal @@aut@@ Peng Zhang @@aut@@ Jeremy Manry @@aut@@ Yoann Seeleuthner @@aut@@ Yu Zhang @@aut@@ Alexandre Bolze @@aut@@ Matthieu Chaldebas @@aut@@ Baptiste Milisavljevic @@aut@@ Adrian Gervais @@aut@@ Paul Bastard @@aut@@ Takaki Asano @@aut@@ Lucy Bizien @@aut@@ Federica Barzaghi @@aut@@ Hassan Abolhassani @@aut@@ Ahmad Abou Tayoun @@aut@@ Alessandro Aiuti @@aut@@ Ilad Alavi Darazam @@aut@@ Luis M. Allende @@aut@@ Rebeca Alonso-Arias @@aut@@ Andrés Augusto Arias @@aut@@ Gokhan Aytekin @@aut@@ Peter Bergman @@aut@@ Simone Bondesan @@aut@@ Yenan T. Bryceson @@aut@@ Ingrid G. Bustos @@aut@@ Oscar Cabrera-Marante @@aut@@ Sheila Carcel @@aut@@ Paola Carrera @@aut@@ Giorgio Casari @@aut@@ Khalil Chaïbi @@aut@@ Roger Colobran @@aut@@ Antonio Condino-Neto @@aut@@ Laura E. Covill @@aut@@ Ottavia M. Delmonte @@aut@@ Loubna El Zein @@aut@@ Carlos Flores @@aut@@ Peter K. Gregersen @@aut@@ Marta Gut @@aut@@ Filomeen Haerynck @@aut@@ Rabih Halwani @@aut@@ Selda Hancerli @@aut@@ Lennart Hammarström @@aut@@ Nevin Hatipoğlu @@aut@@ Adem Karbuz @@aut@@ Sevgi Keles @@aut@@ Christèle Kyheng @@aut@@ Rafael Leon-Lopez @@aut@@ Jose Luis Franco @@aut@@ Davood Mansouri @@aut@@ Javier Martinez-Picado @@aut@@ Ozge Metin Akcan @@aut@@ Isabelle Migeotte @@aut@@ Pierre-Emmanuel Morange @@aut@@ Guillaume Morelle @@aut@@ Andrea Martin-Nalda @@aut@@ Giuseppe Novelli @@aut@@ Antonio Novelli @@aut@@ Tayfun Ozcelik @@aut@@ Figen Palabiyik @@aut@@ Qiang Pan-Hammarström @@aut@@ Rebeca Pérez de Diego @@aut@@ Laura Planas-Serra @@aut@@ Daniel E. Pleguezuelo @@aut@@ Carolina Prando @@aut@@ Aurora Pujol @@aut@@ Luis Felipe Reyes @@aut@@ Jacques G. Rivière @@aut@@ Carlos Rodriguez-Gallego @@aut@@ Julian Rojas @@aut@@ Patrizia Rovere-Querini @@aut@@ Agatha Schlüter @@aut@@ Mohammad Shahrooei @@aut@@ Ali Sobh @@aut@@ Pere Soler-Palacin @@aut@@ Yacine Tandjaoui-Lambiotte @@aut@@ Imran Tipu @@aut@@ Cristina Tresoldi @@aut@@ Jesus Troya @@aut@@ Diederik van de Beek @@aut@@ Mayana Zatz @@aut@@ Pawel Zawadzki @@aut@@ Saleh Zaid Al-Muhsen @@aut@@ Mohammed Faraj Alosaimi @@aut@@ Fahad M. Alsohime @@aut@@ Hagit Baris-Feldman @@aut@@ Manish J. Butte @@aut@@ Stefan N. Constantinescu @@aut@@ Megan A. Cooper @@aut@@ Clifton L. Dalgard @@aut@@ Jacques Fellay @@aut@@ James R. Heath @@aut@@ Yu-Lung Lau @@aut@@ Richard P. Lifton @@aut@@ Tom Maniatis @@aut@@ Trine H. Mogensen @@aut@@ Horst von Bernuth @@aut@@ Alban Lermine @@aut@@ Michel Vidaud @@aut@@ Anne Boland @@aut@@ Jean-François Deleuze @@aut@@ Robert Nussbaum @@aut@@ Amanda Kahn-Kirby @@aut@@ France Mentre @@aut@@ Sarah Tubiana @@aut@@ Guy Gorochov @@aut@@ Florence Tubach @@aut@@ Pierre Hausfater @@aut@@ COVID Human Genetic Effort @@aut@@ COVIDeF Study Group @@aut@@ French COVID Cohort Study Group @@aut@@ CoV-Contact Cohort @@aut@@ COVID-STORM Clinicians @@aut@@ COVID Clinicians @@aut@@ Orchestra Working Group @@aut@@ Amsterdam UMC Covid-19 Biobank @@aut@@ NIAID-USUHS COVID Study Group @@aut@@ Isabelle Meyts @@aut@@ Shen-Ying Zhang @@aut@@ Anne Puel @@aut@@ Luigi D. Notarangelo @@aut@@ Stephanie Boisson-Dupuis @@aut@@ Helen C. Su @@aut@@ Bertrand Boisson @@aut@@ Emmanuelle Jouanguy @@aut@@ Jean-Laurent Casanova @@aut@@ Qian Zhang @@aut@@ Laurent Abel @@aut@@ Aurélie Cobat @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	594424275
id	DOAJ089021509
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ089021509</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230505020958.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230505s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13073-023-01173-8</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ089021509</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ86e4db2aa39842caa8f2f5c9e6d95290</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Daniela Matuozzo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rare variants</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">COVID-19</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Immunity</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Type I interferon</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Estelle Talouarn</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Astrid Marchal</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Peng Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jeremy Manry</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yoann Seeleuthner</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yu Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alexandre Bolze</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Matthieu Chaldebas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Baptiste Milisavljevic</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adrian Gervais</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Paul Bastard</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Takaki Asano</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lucy Bizien</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Federica Barzaghi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Hassan Abolhassani</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ahmad Abou Tayoun</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alessandro Aiuti</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ilad Alavi Darazam</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luis M. Allende</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rebeca Alonso-Arias</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Andrés Augusto Arias</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Gokhan Aytekin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Peter Bergman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Simone Bondesan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yenan T. Bryceson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ingrid G. Bustos</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Oscar Cabrera-Marante</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sheila Carcel</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Paola Carrera</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Giorgio Casari</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Khalil Chaïbi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Roger Colobran</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Antonio Condino-Neto</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laura E. Covill</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ottavia M. Delmonte</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Loubna El Zein</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carlos Flores</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Peter K. Gregersen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Marta Gut</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Filomeen Haerynck</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rabih Halwani</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Selda Hancerli</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lennart Hammarström</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nevin Hatipoğlu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adem Karbuz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sevgi Keles</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Christèle Kyheng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rafael Leon-Lopez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jose Luis Franco</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Davood Mansouri</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Javier Martinez-Picado</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ozge Metin Akcan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Isabelle Migeotte</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pierre-Emmanuel Morange</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Guillaume Morelle</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Andrea Martin-Nalda</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Giuseppe Novelli</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Antonio Novelli</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tayfun Ozcelik</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Figen Palabiyik</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Qiang Pan-Hammarström</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rebeca Pérez de Diego</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laura Planas-Serra</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Daniel E. Pleguezuelo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carolina Prando</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Aurora Pujol</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luis Felipe Reyes</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jacques G. Rivière</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carlos Rodriguez-Gallego</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Julian Rojas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Patrizia Rovere-Querini</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Agatha Schlüter</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mohammad Shahrooei</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ali Sobh</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pere Soler-Palacin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yacine Tandjaoui-Lambiotte</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Imran Tipu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Cristina Tresoldi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jesus Troya</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Diederik van de Beek</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mayana Zatz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pawel Zawadzki</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Saleh Zaid Al-Muhsen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mohammed Faraj Alosaimi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fahad M. Alsohime</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Hagit Baris-Feldman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Manish J. Butte</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stefan N. Constantinescu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Megan A. Cooper</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Clifton L. Dalgard</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jacques Fellay</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">James R. Heath</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yu-Lung Lau</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Richard P. Lifton</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tom Maniatis</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Trine H. Mogensen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Horst von Bernuth</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alban Lermine</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Michel Vidaud</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anne Boland</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jean-François Deleuze</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Robert Nussbaum</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amanda Kahn-Kirby</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">France Mentre</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sarah Tubiana</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Guy Gorochov</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Florence Tubach</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pierre Hausfater</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">COVID Human Genetic Effort</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">COVIDeF Study Group</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">French COVID Cohort Study Group</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">CoV-Contact Cohort</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">COVID-STORM Clinicians</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">COVID Clinicians</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Orchestra Working Group</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amsterdam UMC Covid-19 Biobank</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">NIAID-USUHS COVID Study Group</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Isabelle Meyts</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shen-Ying Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anne Puel</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luigi D. Notarangelo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stephanie Boisson-Dupuis</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Helen C. Su</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bertrand Boisson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Emmanuelle Jouanguy</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jean-Laurent Casanova</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Qian Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laurent Abel</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Aurélie Cobat</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Genome Medicine</subfield><subfield code="d">BMC, 2016</subfield><subfield code="g">15(2023), 1, Seite 25</subfield><subfield code="w">(DE-627)594424275</subfield><subfield code="w">(DE-600)2484394-5</subfield><subfield code="x">1756994X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:15</subfield><subfield code="g">year:2023</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:25</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1186/s13073-023-01173-8</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/86e4db2aa39842caa8f2f5c9e6d95290</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1186/s13073-023-01173-8</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1756-994X</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">15</subfield><subfield code="j">2023</subfield><subfield code="e">1</subfield><subfield code="h">25</subfield></datafield></record></collection>
callnumber-first	Q - Science
author	Daniela Matuozzo
spellingShingle	Daniela Matuozzo misc QH426-470 misc Rare variants misc COVID-19 misc Immunity misc Type I interferon misc Medicine misc R misc Genetics Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
authorStr	Daniela Matuozzo
ppnlink_with_tag_str_mv	@@773@@(DE-627)594424275
format	electronic Article
delete_txt_mv	keep
author_role	aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut
collection	DOAJ
remote_str	true
callnumber-label	QH426-470
illustrated	Not Illustrated
issn	1756994X
topic_title	QH426-470 Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19 Rare variants COVID-19 Immunity Type I interferon
topic	misc QH426-470 misc Rare variants misc COVID-19 misc Immunity misc Type I interferon misc Medicine misc R misc Genetics
topic_unstemmed	misc QH426-470 misc Rare variants misc COVID-19 misc Immunity misc Type I interferon misc Medicine misc R misc Genetics
topic_browse	misc QH426-470 misc Rare variants misc COVID-19 misc Immunity misc Type I interferon misc Medicine misc R misc Genetics
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	Genome Medicine
hierarchy_parent_id	594424275
hierarchy_top_title	Genome Medicine
isfreeaccess_txt	true
familylinks_str_mv	(DE-627)594424275 (DE-600)2484394-5
title	Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
ctrlnum	(DE-627)DOAJ089021509 (DE-599)DOAJ86e4db2aa39842caa8f2f5c9e6d95290
title_full	Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
author_sort	Daniela Matuozzo
journal	Genome Medicine
journalStr	Genome Medicine
callnumber-first-code	Q
lang_code	eng
isOA_bool	true
recordtype	marc
publishDateSort	2023
contenttype_str_mv	txt
container_start_page	25
author_browse	Daniela Matuozzo Estelle Talouarn Astrid Marchal Peng Zhang Jeremy Manry Yoann Seeleuthner Yu Zhang Alexandre Bolze Matthieu Chaldebas Baptiste Milisavljevic Adrian Gervais Paul Bastard Takaki Asano Lucy Bizien Federica Barzaghi Hassan Abolhassani Ahmad Abou Tayoun Alessandro Aiuti Ilad Alavi Darazam Luis M. Allende Rebeca Alonso-Arias Andrés Augusto Arias Gokhan Aytekin Peter Bergman Simone Bondesan Yenan T. Bryceson Ingrid G. Bustos Oscar Cabrera-Marante Sheila Carcel Paola Carrera Giorgio Casari Khalil Chaïbi Roger Colobran Antonio Condino-Neto Laura E. Covill Ottavia M. Delmonte Loubna El Zein Carlos Flores Peter K. Gregersen Marta Gut Filomeen Haerynck Rabih Halwani Selda Hancerli Lennart Hammarström Nevin Hatipoğlu Adem Karbuz Sevgi Keles Christèle Kyheng Rafael Leon-Lopez Jose Luis Franco Davood Mansouri Javier Martinez-Picado Ozge Metin Akcan Isabelle Migeotte Pierre-Emmanuel Morange Guillaume Morelle Andrea Martin-Nalda Giuseppe Novelli Antonio Novelli Tayfun Ozcelik Figen Palabiyik Qiang Pan-Hammarström Rebeca Pérez de Diego Laura Planas-Serra Daniel E. Pleguezuelo Carolina Prando Aurora Pujol Luis Felipe Reyes Jacques G. Rivière Carlos Rodriguez-Gallego Julian Rojas Patrizia Rovere-Querini Agatha Schlüter Mohammad Shahrooei Ali Sobh Pere Soler-Palacin Yacine Tandjaoui-Lambiotte Imran Tipu Cristina Tresoldi Jesus Troya Diederik van de Beek Mayana Zatz Pawel Zawadzki Saleh Zaid Al-Muhsen Mohammed Faraj Alosaimi Fahad M. Alsohime Hagit Baris-Feldman Manish J. Butte Stefan N. Constantinescu Megan A. Cooper Clifton L. Dalgard Jacques Fellay James R. Heath Yu-Lung Lau Richard P. Lifton Tom Maniatis Trine H. Mogensen Horst von Bernuth Alban Lermine Michel Vidaud Anne Boland Jean-François Deleuze Robert Nussbaum Amanda Kahn-Kirby France Mentre Sarah Tubiana Guy Gorochov Florence Tubach Pierre Hausfater COVID Human Genetic Effort COVIDeF Study Group French COVID Cohort Study Group CoV-Contact Cohort COVID-STORM Clinicians COVID Clinicians Orchestra Working Group Amsterdam UMC Covid-19 Biobank NIAID-USUHS COVID Study Group Isabelle Meyts Shen-Ying Zhang Anne Puel Luigi D. Notarangelo Stephanie Boisson-Dupuis Helen C. Su Bertrand Boisson Emmanuelle Jouanguy Jean-Laurent Casanova Qian Zhang Laurent Abel Aurélie Cobat
container_volume	15
class	QH426-470
format_se	Elektronische Aufsätze
author-letter	Daniela Matuozzo
doi_str_mv	10.1186/s13073-023-01173-8
author2-role	verfasserin
title_sort	rare predicted loss-of-function variants of type i ifn immunity genes are associated with life-threatening covid-19
callnumber	QH426-470
title_auth	Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
abstract	Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
abstractGer	Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
abstract_unstemmed	Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
container_issue	1
title_short	Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
url	https://doi.org/10.1186/s13073-023-01173-8 https://doaj.org/article/86e4db2aa39842caa8f2f5c9e6d95290 https://doaj.org/toc/1756-994X
remote_bool	true
author2	Estelle Talouarn Astrid Marchal Peng Zhang Jeremy Manry Yoann Seeleuthner Yu Zhang Alexandre Bolze Matthieu Chaldebas Baptiste Milisavljevic Adrian Gervais Paul Bastard Takaki Asano Lucy Bizien Federica Barzaghi Hassan Abolhassani Ahmad Abou Tayoun Alessandro Aiuti Ilad Alavi Darazam Luis M. Allende Rebeca Alonso-Arias Andrés Augusto Arias Gokhan Aytekin Peter Bergman Simone Bondesan Yenan T. Bryceson Ingrid G. Bustos Oscar Cabrera-Marante Sheila Carcel Paola Carrera Giorgio Casari Khalil Chaïbi Roger Colobran Antonio Condino-Neto Laura E. Covill Ottavia M. Delmonte Loubna El Zein Carlos Flores Peter K. Gregersen Marta Gut Filomeen Haerynck Rabih Halwani Selda Hancerli Lennart Hammarström Nevin Hatipoğlu Adem Karbuz Sevgi Keles Christèle Kyheng Rafael Leon-Lopez Jose Luis Franco Davood Mansouri Javier Martinez-Picado Ozge Metin Akcan Isabelle Migeotte Pierre-Emmanuel Morange Guillaume Morelle Andrea Martin-Nalda Giuseppe Novelli Antonio Novelli Tayfun Ozcelik Figen Palabiyik Qiang Pan-Hammarström Rebeca Pérez de Diego Laura Planas-Serra Daniel E. Pleguezuelo Carolina Prando Aurora Pujol Luis Felipe Reyes Jacques G. Rivière Carlos Rodriguez-Gallego Julian Rojas Patrizia Rovere-Querini Agatha Schlüter Mohammad Shahrooei Ali Sobh Pere Soler-Palacin Yacine Tandjaoui-Lambiotte Imran Tipu Cristina Tresoldi Jesus Troya Diederik van de Beek Mayana Zatz Pawel Zawadzki Saleh Zaid Al-Muhsen Mohammed Faraj Alosaimi Fahad M. Alsohime Hagit Baris-Feldman Manish J. Butte Stefan N. Constantinescu Megan A. Cooper Clifton L. Dalgard Jacques Fellay James R. Heath Yu-Lung Lau Richard P. Lifton Tom Maniatis Trine H. Mogensen Horst von Bernuth Alban Lermine Michel Vidaud Anne Boland Jean-François Deleuze Robert Nussbaum Amanda Kahn-Kirby France Mentre Sarah Tubiana Guy Gorochov Florence Tubach Pierre Hausfater COVID Human Genetic Effort COVIDeF Study Group French COVID Cohort Study Group CoV-Contact Cohort COVID-STORM Clinicians COVID Clinicians Orchestra Working Group Amsterdam UMC Covid-19 Biobank NIAID-USUHS COVID Study Group Isabelle Meyts Shen-Ying Zhang Anne Puel Luigi D. Notarangelo Stephanie Boisson-Dupuis Helen C. Su Bertrand Boisson Emmanuelle Jouanguy Jean-Laurent Casanova Qian Zhang Laurent Abel Aurélie Cobat
author2Str	Estelle Talouarn Astrid Marchal Peng Zhang Jeremy Manry Yoann Seeleuthner Yu Zhang Alexandre Bolze Matthieu Chaldebas Baptiste Milisavljevic Adrian Gervais Paul Bastard Takaki Asano Lucy Bizien Federica Barzaghi Hassan Abolhassani Ahmad Abou Tayoun Alessandro Aiuti Ilad Alavi Darazam Luis M. Allende Rebeca Alonso-Arias Andrés Augusto Arias Gokhan Aytekin Peter Bergman Simone Bondesan Yenan T. Bryceson Ingrid G. Bustos Oscar Cabrera-Marante Sheila Carcel Paola Carrera Giorgio Casari Khalil Chaïbi Roger Colobran Antonio Condino-Neto Laura E. Covill Ottavia M. Delmonte Loubna El Zein Carlos Flores Peter K. Gregersen Marta Gut Filomeen Haerynck Rabih Halwani Selda Hancerli Lennart Hammarström Nevin Hatipoğlu Adem Karbuz Sevgi Keles Christèle Kyheng Rafael Leon-Lopez Jose Luis Franco Davood Mansouri Javier Martinez-Picado Ozge Metin Akcan Isabelle Migeotte Pierre-Emmanuel Morange Guillaume Morelle Andrea Martin-Nalda Giuseppe Novelli Antonio Novelli Tayfun Ozcelik Figen Palabiyik Qiang Pan-Hammarström Rebeca Pérez de Diego Laura Planas-Serra Daniel E. Pleguezuelo Carolina Prando Aurora Pujol Luis Felipe Reyes Jacques G. Rivière Carlos Rodriguez-Gallego Julian Rojas Patrizia Rovere-Querini Agatha Schlüter Mohammad Shahrooei Ali Sobh Pere Soler-Palacin Yacine Tandjaoui-Lambiotte Imran Tipu Cristina Tresoldi Jesus Troya Diederik van de Beek Mayana Zatz Pawel Zawadzki Saleh Zaid Al-Muhsen Mohammed Faraj Alosaimi Fahad M. Alsohime Hagit Baris-Feldman Manish J. Butte Stefan N. Constantinescu Megan A. Cooper Clifton L. Dalgard Jacques Fellay James R. Heath Yu-Lung Lau Richard P. Lifton Tom Maniatis Trine H. Mogensen Horst von Bernuth Alban Lermine Michel Vidaud Anne Boland Jean-François Deleuze Robert Nussbaum Amanda Kahn-Kirby France Mentre Sarah Tubiana Guy Gorochov Florence Tubach Pierre Hausfater COVID Human Genetic Effort COVIDeF Study Group French COVID Cohort Study Group CoV-Contact Cohort COVID-STORM Clinicians COVID Clinicians Orchestra Working Group Amsterdam UMC Covid-19 Biobank NIAID-USUHS COVID Study Group Isabelle Meyts Shen-Ying Zhang Anne Puel Luigi D. Notarangelo Stephanie Boisson-Dupuis Helen C. Su Bertrand Boisson Emmanuelle Jouanguy Jean-Laurent Casanova Qian Zhang Laurent Abel Aurélie Cobat
ppnlink	594424275
callnumber-subject	QH - Natural History and Biology
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.1186/s13073-023-01173-8
callnumber-a	QH426-470
up_date	2024-07-03T20:47:55.939Z
_version_	1803592323269918723
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ089021509</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230505020958.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230505s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13073-023-01173-8</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ089021509</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ86e4db2aa39842caa8f2f5c9e6d95290</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Daniela Matuozzo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rare variants</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">COVID-19</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Immunity</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Type I interferon</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Estelle Talouarn</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Astrid Marchal</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Peng Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jeremy Manry</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yoann Seeleuthner</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yu Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alexandre Bolze</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Matthieu Chaldebas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Baptiste Milisavljevic</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adrian Gervais</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Paul Bastard</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Takaki Asano</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lucy Bizien</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Federica Barzaghi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Hassan Abolhassani</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ahmad Abou Tayoun</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alessandro Aiuti</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ilad Alavi Darazam</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luis M. Allende</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rebeca Alonso-Arias</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Andrés Augusto Arias</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Gokhan Aytekin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Peter Bergman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Simone Bondesan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yenan T. Bryceson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ingrid G. Bustos</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Oscar Cabrera-Marante</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sheila Carcel</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Paola Carrera</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Giorgio Casari</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Khalil Chaïbi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Roger Colobran</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Antonio Condino-Neto</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laura E. Covill</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ottavia M. Delmonte</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Loubna El Zein</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carlos Flores</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Peter K. Gregersen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Marta Gut</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Filomeen Haerynck</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rabih Halwani</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Selda Hancerli</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Lennart Hammarström</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nevin Hatipoğlu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adem Karbuz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sevgi Keles</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Christèle Kyheng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rafael Leon-Lopez</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jose Luis Franco</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Davood Mansouri</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Javier Martinez-Picado</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ozge Metin Akcan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Isabelle Migeotte</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pierre-Emmanuel Morange</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Guillaume Morelle</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Andrea Martin-Nalda</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Giuseppe Novelli</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Antonio Novelli</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tayfun Ozcelik</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Figen Palabiyik</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Qiang Pan-Hammarström</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rebeca Pérez de Diego</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laura Planas-Serra</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Daniel E. Pleguezuelo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carolina Prando</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Aurora Pujol</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luis Felipe Reyes</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jacques G. Rivière</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carlos Rodriguez-Gallego</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Julian Rojas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Patrizia Rovere-Querini</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Agatha Schlüter</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mohammad Shahrooei</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Ali Sobh</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pere Soler-Palacin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yacine Tandjaoui-Lambiotte</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Imran Tipu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Cristina Tresoldi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jesus Troya</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Diederik van de Beek</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mayana Zatz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pawel Zawadzki</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Saleh Zaid Al-Muhsen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mohammed Faraj Alosaimi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fahad M. Alsohime</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Hagit Baris-Feldman</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Manish J. Butte</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stefan N. Constantinescu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Megan A. Cooper</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Clifton L. Dalgard</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jacques Fellay</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">James R. Heath</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yu-Lung Lau</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Richard P. Lifton</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tom Maniatis</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Trine H. Mogensen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Horst von Bernuth</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Alban Lermine</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Michel Vidaud</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anne Boland</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jean-François Deleuze</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Robert Nussbaum</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amanda Kahn-Kirby</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">France Mentre</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sarah Tubiana</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Guy Gorochov</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Florence Tubach</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pierre Hausfater</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">COVID Human Genetic Effort</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">COVIDeF Study Group</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">French COVID Cohort Study Group</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">CoV-Contact Cohort</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">COVID-STORM Clinicians</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">COVID Clinicians</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Orchestra Working Group</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Amsterdam UMC Covid-19 Biobank</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">NIAID-USUHS COVID Study Group</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Isabelle Meyts</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Shen-Ying Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anne Puel</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luigi D. Notarangelo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Stephanie Boisson-Dupuis</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Helen C. Su</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bertrand Boisson</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Emmanuelle Jouanguy</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jean-Laurent Casanova</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Qian Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laurent Abel</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Aurélie Cobat</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Genome Medicine</subfield><subfield code="d">BMC, 2016</subfield><subfield code="g">15(2023), 1, Seite 25</subfield><subfield code="w">(DE-627)594424275</subfield><subfield code="w">(DE-600)2484394-5</subfield><subfield code="x">1756994X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:15</subfield><subfield code="g">year:2023</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:25</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1186/s13073-023-01173-8</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/86e4db2aa39842caa8f2f5c9e6d95290</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1186/s13073-023-01173-8</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1756-994X</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">15</subfield><subfield code="j">2023</subfield><subfield code="e">1</subfield><subfield code="h">25</subfield></datafield></record></collection>
score	7.4031916

Nicht das Richtige dabei?

Schreiben Sie uns!

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?