HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed...
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Autor*in:	Sigrid Le Clerc [verfasserIn] Laura Lombardi [verfasserIn] Bernhard T. Baune [verfasserIn] Azmeraw T. Amare [verfasserIn] Klaus Oliver Schubert [verfasserIn] Liping Hou [verfasserIn] Scott R. Clark [verfasserIn] Sergi Papiol [verfasserIn] Micah Cearns [verfasserIn] Urs Heilbronner [verfasserIn] Franziska Degenhardt [verfasserIn] Fasil Tekola-Ayele [verfasserIn] Yi-Hsiang Hsu [verfasserIn] Tatyana Shekhtman [verfasserIn] Mazda Adli [verfasserIn] Nirmala Akula [verfasserIn] Kazufumi Akiyama [verfasserIn] Raffaella Ardau [verfasserIn] Bárbara Arias [verfasserIn] Jean-Michel Aubry [verfasserIn] Lena Backlund [verfasserIn] Abesh Kumar Bhattacharjee [verfasserIn] Frank Bellivier [verfasserIn] Antonio Benabarre [verfasserIn] Susanne Bengesser [verfasserIn] Joanna M. Biernacka [verfasserIn] Armin Birner [verfasserIn] Clara Brichant-Petitjean [verfasserIn] Pablo Cervantes [verfasserIn] Hsi-Chung Chen [verfasserIn] Caterina Chillotti [verfasserIn] Sven Cichon [verfasserIn] Cristiana Cruceanu [verfasserIn] Piotr M. Czerski [verfasserIn] Nina Dalkner [verfasserIn] Alexandre Dayer [verfasserIn] Maria Del Zompo [verfasserIn] J. Raymond DePaulo [verfasserIn] Bruno Étain [verfasserIn] Stephane Jamain [verfasserIn] Peter Falkai [verfasserIn] Andreas J. Forstner [verfasserIn] Louise Frisen [verfasserIn] Mark A. Frye [verfasserIn] Janice M. Fullerton [verfasserIn] Sébastien Gard [verfasserIn] Julie S. Garnham [verfasserIn] Fernando S. Goes [verfasserIn] Maria Grigoroiu-Serbanescu [verfasserIn] Paul Grof [verfasserIn] Ryota Hashimoto [verfasserIn] Joanna Hauser [verfasserIn] Stefan Herms [verfasserIn] Per Hoffmann [verfasserIn] Esther Jiménez [verfasserIn] Jean-Pierre Kahn [verfasserIn] Layla Kassem [verfasserIn] Po-Hsiu Kuo [verfasserIn] Tadafumi Kato [verfasserIn] John R. Kelsoe [verfasserIn] Sarah Kittel-Schneider [verfasserIn] Ewa Ferensztajn-Rochowiak [verfasserIn] Barbara König [verfasserIn] Ichiro Kusumi [verfasserIn] Gonzalo Laje [verfasserIn] Mikael Landén [verfasserIn] Catharina Lavebratt [verfasserIn] Susan G. Leckband [verfasserIn] Alfonso Tortorella [verfasserIn] Mirko Manchia [verfasserIn] Lina Martinsson [verfasserIn] Michael J. McCarthy [verfasserIn] Susan L. McElroy [verfasserIn] Francesc Colom [verfasserIn] Vincent Millischer [verfasserIn] Marina Mitjans [verfasserIn] Francis M. Mondimore [verfasserIn] Palmiero Monteleone [verfasserIn] Caroline M. Nievergelt [verfasserIn] Markus M. Nöthen [verfasserIn] Tomas Novák [verfasserIn] Claire O’Donovan [verfasserIn] Norio Ozaki [verfasserIn] Urban Ösby [verfasserIn] Andrea Pfennig [verfasserIn] James B. Potash [verfasserIn] Andreas Reif [verfasserIn] Eva Reininghaus [verfasserIn] Guy A. Rouleau [verfasserIn] Janusz K. Rybakowski [verfasserIn] Martin Schalling [verfasserIn] Peter R. Schofield [verfasserIn] Barbara W. Schweizer [verfasserIn] Giovanni Severino [verfasserIn] Paul D. Shilling [verfasserIn] Katzutaka Shimoda [verfasserIn] Christian Simhandl [verfasserIn] Claire M. Slaney [verfasserIn] Claudia Pisanu [verfasserIn] Alessio Squassina [verfasserIn] Thomas Stamm [verfasserIn] Pavla Stopkova [verfasserIn] Mario Maj [verfasserIn] Gustavo Turecki [verfasserIn] Eduard Vieta [verfasserIn] Julia Veeh [verfasserIn] Stephanie H. Witt [verfasserIn] Adam Wright [verfasserIn] Peter P. Zandi [verfasserIn] Philip B. Mitchell [verfasserIn] Michael Bauer [verfasserIn] Martin Alda [verfasserIn] Marcella Rietschel [verfasserIn] Francis J. McMahon [verfasserIn] Thomas G. Schulze [verfasserIn] Jean-Louis Spadoni [verfasserIn] Wahid Boukouaci [verfasserIn] Jean-Romain Richard [verfasserIn] Philippe Le Corvoisier [verfasserIn] Caroline Barrau [verfasserIn] Jean-François Zagury [verfasserIn] Marion Leboyer [verfasserIn] Ryad Tamouza [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Übergeordnetes Werk:	In: Scientific Reports - Nature Portfolio, 2011, 11(2021), 1, Seite 12
Übergeordnetes Werk:	volume:11 ; year:2021 ; number:1 ; pages:12

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41598-021-97140-7

Katalog-ID:	DOAJ052704718

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520			\|a Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
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allfields	10.1038/s41598-021-97140-7 doi (DE-627)DOAJ052704718 (DE-599)DOAJcd2b00abcda74c64ac98ae9090e72898 DE-627 ger DE-627 rakwb eng Sigrid Le Clerc verfasserin aut HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response. Medicine R Science Q Laura Lombardi verfasserin aut Bernhard T. Baune verfasserin aut Azmeraw T. Amare verfasserin aut Klaus Oliver Schubert verfasserin aut Liping Hou verfasserin aut Scott R. Clark verfasserin aut Sergi Papiol verfasserin aut Micah Cearns verfasserin aut Urs Heilbronner verfasserin aut Franziska Degenhardt verfasserin aut Fasil Tekola-Ayele verfasserin aut Yi-Hsiang Hsu verfasserin aut Tatyana Shekhtman verfasserin aut Mazda Adli verfasserin aut Nirmala Akula verfasserin aut Kazufumi Akiyama verfasserin aut Raffaella Ardau verfasserin aut Bárbara Arias verfasserin aut Jean-Michel Aubry verfasserin aut Lena Backlund verfasserin aut Abesh Kumar Bhattacharjee verfasserin aut Frank Bellivier verfasserin aut Antonio Benabarre verfasserin aut Susanne Bengesser verfasserin aut Joanna M. Biernacka verfasserin aut Armin Birner verfasserin aut Clara Brichant-Petitjean verfasserin aut Pablo Cervantes verfasserin aut Hsi-Chung Chen verfasserin aut Caterina Chillotti verfasserin aut Sven Cichon verfasserin aut Cristiana Cruceanu verfasserin aut Piotr M. Czerski verfasserin aut Nina Dalkner verfasserin aut Alexandre Dayer verfasserin aut Maria Del Zompo verfasserin aut J. Raymond DePaulo verfasserin aut Bruno Étain verfasserin aut Stephane Jamain verfasserin aut Peter Falkai verfasserin aut Andreas J. Forstner verfasserin aut Louise Frisen verfasserin aut Mark A. Frye verfasserin aut Janice M. Fullerton verfasserin aut Sébastien Gard verfasserin aut Julie S. Garnham verfasserin aut Fernando S. Goes verfasserin aut Maria Grigoroiu-Serbanescu verfasserin aut Paul Grof verfasserin aut Ryota Hashimoto verfasserin aut Joanna Hauser verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Esther Jiménez verfasserin aut Jean-Pierre Kahn verfasserin aut Layla Kassem verfasserin aut Po-Hsiu Kuo verfasserin aut Tadafumi Kato verfasserin aut John R. Kelsoe verfasserin aut Sarah Kittel-Schneider verfasserin aut Ewa Ferensztajn-Rochowiak verfasserin aut Barbara König verfasserin aut Ichiro Kusumi verfasserin aut Gonzalo Laje verfasserin aut Mikael Landén verfasserin aut Catharina Lavebratt verfasserin aut Susan G. Leckband verfasserin aut Alfonso Tortorella verfasserin aut Mirko Manchia verfasserin aut Lina Martinsson verfasserin aut Michael J. McCarthy verfasserin aut Susan L. McElroy verfasserin aut Francesc Colom verfasserin aut Vincent Millischer verfasserin aut Marina Mitjans verfasserin aut Francis M. Mondimore verfasserin aut Palmiero Monteleone verfasserin aut Caroline M. Nievergelt verfasserin aut Markus M. Nöthen verfasserin aut Tomas Novák verfasserin aut Claire O’Donovan verfasserin aut Norio Ozaki verfasserin aut Urban Ösby verfasserin aut Andrea Pfennig verfasserin aut James B. Potash verfasserin aut Andreas Reif verfasserin aut Eva Reininghaus verfasserin aut Guy A. Rouleau verfasserin aut Janusz K. Rybakowski verfasserin aut Martin Schalling verfasserin aut Peter R. Schofield verfasserin aut Barbara W. Schweizer verfasserin aut Giovanni Severino verfasserin aut Paul D. Shilling verfasserin aut Katzutaka Shimoda verfasserin aut Christian Simhandl verfasserin aut Claire M. Slaney verfasserin aut Claudia Pisanu verfasserin aut Alessio Squassina verfasserin aut Thomas Stamm verfasserin aut Pavla Stopkova verfasserin aut Mario Maj verfasserin aut Gustavo Turecki verfasserin aut Eduard Vieta verfasserin aut Julia Veeh verfasserin aut Stephanie H. Witt verfasserin aut Adam Wright verfasserin aut Peter P. Zandi verfasserin aut Philip B. Mitchell verfasserin aut Michael Bauer verfasserin aut Martin Alda verfasserin aut Marcella Rietschel verfasserin aut Francis J. McMahon verfasserin aut Thomas G. Schulze verfasserin aut Jean-Louis Spadoni verfasserin aut Wahid Boukouaci verfasserin aut Jean-Romain Richard verfasserin aut Philippe Le Corvoisier verfasserin aut Caroline Barrau verfasserin aut Jean-François Zagury verfasserin aut Marion Leboyer verfasserin aut Ryad Tamouza verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 12 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:12 https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/article/cd2b00abcda74c64ac98ae9090e72898 kostenfrei https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/toc/2045-2322 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_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 12
spelling	10.1038/s41598-021-97140-7 doi (DE-627)DOAJ052704718 (DE-599)DOAJcd2b00abcda74c64ac98ae9090e72898 DE-627 ger DE-627 rakwb eng Sigrid Le Clerc verfasserin aut HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response. Medicine R Science Q Laura Lombardi verfasserin aut Bernhard T. Baune verfasserin aut Azmeraw T. Amare verfasserin aut Klaus Oliver Schubert verfasserin aut Liping Hou verfasserin aut Scott R. Clark verfasserin aut Sergi Papiol verfasserin aut Micah Cearns verfasserin aut Urs Heilbronner verfasserin aut Franziska Degenhardt verfasserin aut Fasil Tekola-Ayele verfasserin aut Yi-Hsiang Hsu verfasserin aut Tatyana Shekhtman verfasserin aut Mazda Adli verfasserin aut Nirmala Akula verfasserin aut Kazufumi Akiyama verfasserin aut Raffaella Ardau verfasserin aut Bárbara Arias verfasserin aut Jean-Michel Aubry verfasserin aut Lena Backlund verfasserin aut Abesh Kumar Bhattacharjee verfasserin aut Frank Bellivier verfasserin aut Antonio Benabarre verfasserin aut Susanne Bengesser verfasserin aut Joanna M. Biernacka verfasserin aut Armin Birner verfasserin aut Clara Brichant-Petitjean verfasserin aut Pablo Cervantes verfasserin aut Hsi-Chung Chen verfasserin aut Caterina Chillotti verfasserin aut Sven Cichon verfasserin aut Cristiana Cruceanu verfasserin aut Piotr M. Czerski verfasserin aut Nina Dalkner verfasserin aut Alexandre Dayer verfasserin aut Maria Del Zompo verfasserin aut J. Raymond DePaulo verfasserin aut Bruno Étain verfasserin aut Stephane Jamain verfasserin aut Peter Falkai verfasserin aut Andreas J. Forstner verfasserin aut Louise Frisen verfasserin aut Mark A. Frye verfasserin aut Janice M. Fullerton verfasserin aut Sébastien Gard verfasserin aut Julie S. Garnham verfasserin aut Fernando S. Goes verfasserin aut Maria Grigoroiu-Serbanescu verfasserin aut Paul Grof verfasserin aut Ryota Hashimoto verfasserin aut Joanna Hauser verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Esther Jiménez verfasserin aut Jean-Pierre Kahn verfasserin aut Layla Kassem verfasserin aut Po-Hsiu Kuo verfasserin aut Tadafumi Kato verfasserin aut John R. Kelsoe verfasserin aut Sarah Kittel-Schneider verfasserin aut Ewa Ferensztajn-Rochowiak verfasserin aut Barbara König verfasserin aut Ichiro Kusumi verfasserin aut Gonzalo Laje verfasserin aut Mikael Landén verfasserin aut Catharina Lavebratt verfasserin aut Susan G. Leckband verfasserin aut Alfonso Tortorella verfasserin aut Mirko Manchia verfasserin aut Lina Martinsson verfasserin aut Michael J. McCarthy verfasserin aut Susan L. McElroy verfasserin aut Francesc Colom verfasserin aut Vincent Millischer verfasserin aut Marina Mitjans verfasserin aut Francis M. Mondimore verfasserin aut Palmiero Monteleone verfasserin aut Caroline M. Nievergelt verfasserin aut Markus M. Nöthen verfasserin aut Tomas Novák verfasserin aut Claire O’Donovan verfasserin aut Norio Ozaki verfasserin aut Urban Ösby verfasserin aut Andrea Pfennig verfasserin aut James B. Potash verfasserin aut Andreas Reif verfasserin aut Eva Reininghaus verfasserin aut Guy A. Rouleau verfasserin aut Janusz K. Rybakowski verfasserin aut Martin Schalling verfasserin aut Peter R. Schofield verfasserin aut Barbara W. Schweizer verfasserin aut Giovanni Severino verfasserin aut Paul D. Shilling verfasserin aut Katzutaka Shimoda verfasserin aut Christian Simhandl verfasserin aut Claire M. Slaney verfasserin aut Claudia Pisanu verfasserin aut Alessio Squassina verfasserin aut Thomas Stamm verfasserin aut Pavla Stopkova verfasserin aut Mario Maj verfasserin aut Gustavo Turecki verfasserin aut Eduard Vieta verfasserin aut Julia Veeh verfasserin aut Stephanie H. Witt verfasserin aut Adam Wright verfasserin aut Peter P. Zandi verfasserin aut Philip B. Mitchell verfasserin aut Michael Bauer verfasserin aut Martin Alda verfasserin aut Marcella Rietschel verfasserin aut Francis J. McMahon verfasserin aut Thomas G. Schulze verfasserin aut Jean-Louis Spadoni verfasserin aut Wahid Boukouaci verfasserin aut Jean-Romain Richard verfasserin aut Philippe Le Corvoisier verfasserin aut Caroline Barrau verfasserin aut Jean-François Zagury verfasserin aut Marion Leboyer verfasserin aut Ryad Tamouza verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 12 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:12 https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/article/cd2b00abcda74c64ac98ae9090e72898 kostenfrei https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/toc/2045-2322 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_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 12
allfields_unstemmed	10.1038/s41598-021-97140-7 doi (DE-627)DOAJ052704718 (DE-599)DOAJcd2b00abcda74c64ac98ae9090e72898 DE-627 ger DE-627 rakwb eng Sigrid Le Clerc verfasserin aut HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response. Medicine R Science Q Laura Lombardi verfasserin aut Bernhard T. Baune verfasserin aut Azmeraw T. Amare verfasserin aut Klaus Oliver Schubert verfasserin aut Liping Hou verfasserin aut Scott R. Clark verfasserin aut Sergi Papiol verfasserin aut Micah Cearns verfasserin aut Urs Heilbronner verfasserin aut Franziska Degenhardt verfasserin aut Fasil Tekola-Ayele verfasserin aut Yi-Hsiang Hsu verfasserin aut Tatyana Shekhtman verfasserin aut Mazda Adli verfasserin aut Nirmala Akula verfasserin aut Kazufumi Akiyama verfasserin aut Raffaella Ardau verfasserin aut Bárbara Arias verfasserin aut Jean-Michel Aubry verfasserin aut Lena Backlund verfasserin aut Abesh Kumar Bhattacharjee verfasserin aut Frank Bellivier verfasserin aut Antonio Benabarre verfasserin aut Susanne Bengesser verfasserin aut Joanna M. Biernacka verfasserin aut Armin Birner verfasserin aut Clara Brichant-Petitjean verfasserin aut Pablo Cervantes verfasserin aut Hsi-Chung Chen verfasserin aut Caterina Chillotti verfasserin aut Sven Cichon verfasserin aut Cristiana Cruceanu verfasserin aut Piotr M. Czerski verfasserin aut Nina Dalkner verfasserin aut Alexandre Dayer verfasserin aut Maria Del Zompo verfasserin aut J. Raymond DePaulo verfasserin aut Bruno Étain verfasserin aut Stephane Jamain verfasserin aut Peter Falkai verfasserin aut Andreas J. Forstner verfasserin aut Louise Frisen verfasserin aut Mark A. Frye verfasserin aut Janice M. Fullerton verfasserin aut Sébastien Gard verfasserin aut Julie S. Garnham verfasserin aut Fernando S. Goes verfasserin aut Maria Grigoroiu-Serbanescu verfasserin aut Paul Grof verfasserin aut Ryota Hashimoto verfasserin aut Joanna Hauser verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Esther Jiménez verfasserin aut Jean-Pierre Kahn verfasserin aut Layla Kassem verfasserin aut Po-Hsiu Kuo verfasserin aut Tadafumi Kato verfasserin aut John R. Kelsoe verfasserin aut Sarah Kittel-Schneider verfasserin aut Ewa Ferensztajn-Rochowiak verfasserin aut Barbara König verfasserin aut Ichiro Kusumi verfasserin aut Gonzalo Laje verfasserin aut Mikael Landén verfasserin aut Catharina Lavebratt verfasserin aut Susan G. Leckband verfasserin aut Alfonso Tortorella verfasserin aut Mirko Manchia verfasserin aut Lina Martinsson verfasserin aut Michael J. McCarthy verfasserin aut Susan L. McElroy verfasserin aut Francesc Colom verfasserin aut Vincent Millischer verfasserin aut Marina Mitjans verfasserin aut Francis M. Mondimore verfasserin aut Palmiero Monteleone verfasserin aut Caroline M. Nievergelt verfasserin aut Markus M. Nöthen verfasserin aut Tomas Novák verfasserin aut Claire O’Donovan verfasserin aut Norio Ozaki verfasserin aut Urban Ösby verfasserin aut Andrea Pfennig verfasserin aut James B. Potash verfasserin aut Andreas Reif verfasserin aut Eva Reininghaus verfasserin aut Guy A. Rouleau verfasserin aut Janusz K. Rybakowski verfasserin aut Martin Schalling verfasserin aut Peter R. Schofield verfasserin aut Barbara W. Schweizer verfasserin aut Giovanni Severino verfasserin aut Paul D. Shilling verfasserin aut Katzutaka Shimoda verfasserin aut Christian Simhandl verfasserin aut Claire M. Slaney verfasserin aut Claudia Pisanu verfasserin aut Alessio Squassina verfasserin aut Thomas Stamm verfasserin aut Pavla Stopkova verfasserin aut Mario Maj verfasserin aut Gustavo Turecki verfasserin aut Eduard Vieta verfasserin aut Julia Veeh verfasserin aut Stephanie H. Witt verfasserin aut Adam Wright verfasserin aut Peter P. Zandi verfasserin aut Philip B. Mitchell verfasserin aut Michael Bauer verfasserin aut Martin Alda verfasserin aut Marcella Rietschel verfasserin aut Francis J. McMahon verfasserin aut Thomas G. Schulze verfasserin aut Jean-Louis Spadoni verfasserin aut Wahid Boukouaci verfasserin aut Jean-Romain Richard verfasserin aut Philippe Le Corvoisier verfasserin aut Caroline Barrau verfasserin aut Jean-François Zagury verfasserin aut Marion Leboyer verfasserin aut Ryad Tamouza verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 12 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:12 https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/article/cd2b00abcda74c64ac98ae9090e72898 kostenfrei https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/toc/2045-2322 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_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 12
allfieldsGer	10.1038/s41598-021-97140-7 doi (DE-627)DOAJ052704718 (DE-599)DOAJcd2b00abcda74c64ac98ae9090e72898 DE-627 ger DE-627 rakwb eng Sigrid Le Clerc verfasserin aut HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response. Medicine R Science Q Laura Lombardi verfasserin aut Bernhard T. Baune verfasserin aut Azmeraw T. Amare verfasserin aut Klaus Oliver Schubert verfasserin aut Liping Hou verfasserin aut Scott R. Clark verfasserin aut Sergi Papiol verfasserin aut Micah Cearns verfasserin aut Urs Heilbronner verfasserin aut Franziska Degenhardt verfasserin aut Fasil Tekola-Ayele verfasserin aut Yi-Hsiang Hsu verfasserin aut Tatyana Shekhtman verfasserin aut Mazda Adli verfasserin aut Nirmala Akula verfasserin aut Kazufumi Akiyama verfasserin aut Raffaella Ardau verfasserin aut Bárbara Arias verfasserin aut Jean-Michel Aubry verfasserin aut Lena Backlund verfasserin aut Abesh Kumar Bhattacharjee verfasserin aut Frank Bellivier verfasserin aut Antonio Benabarre verfasserin aut Susanne Bengesser verfasserin aut Joanna M. Biernacka verfasserin aut Armin Birner verfasserin aut Clara Brichant-Petitjean verfasserin aut Pablo Cervantes verfasserin aut Hsi-Chung Chen verfasserin aut Caterina Chillotti verfasserin aut Sven Cichon verfasserin aut Cristiana Cruceanu verfasserin aut Piotr M. Czerski verfasserin aut Nina Dalkner verfasserin aut Alexandre Dayer verfasserin aut Maria Del Zompo verfasserin aut J. Raymond DePaulo verfasserin aut Bruno Étain verfasserin aut Stephane Jamain verfasserin aut Peter Falkai verfasserin aut Andreas J. Forstner verfasserin aut Louise Frisen verfasserin aut Mark A. Frye verfasserin aut Janice M. Fullerton verfasserin aut Sébastien Gard verfasserin aut Julie S. Garnham verfasserin aut Fernando S. Goes verfasserin aut Maria Grigoroiu-Serbanescu verfasserin aut Paul Grof verfasserin aut Ryota Hashimoto verfasserin aut Joanna Hauser verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Esther Jiménez verfasserin aut Jean-Pierre Kahn verfasserin aut Layla Kassem verfasserin aut Po-Hsiu Kuo verfasserin aut Tadafumi Kato verfasserin aut John R. Kelsoe verfasserin aut Sarah Kittel-Schneider verfasserin aut Ewa Ferensztajn-Rochowiak verfasserin aut Barbara König verfasserin aut Ichiro Kusumi verfasserin aut Gonzalo Laje verfasserin aut Mikael Landén verfasserin aut Catharina Lavebratt verfasserin aut Susan G. Leckband verfasserin aut Alfonso Tortorella verfasserin aut Mirko Manchia verfasserin aut Lina Martinsson verfasserin aut Michael J. McCarthy verfasserin aut Susan L. McElroy verfasserin aut Francesc Colom verfasserin aut Vincent Millischer verfasserin aut Marina Mitjans verfasserin aut Francis M. Mondimore verfasserin aut Palmiero Monteleone verfasserin aut Caroline M. Nievergelt verfasserin aut Markus M. Nöthen verfasserin aut Tomas Novák verfasserin aut Claire O’Donovan verfasserin aut Norio Ozaki verfasserin aut Urban Ösby verfasserin aut Andrea Pfennig verfasserin aut James B. Potash verfasserin aut Andreas Reif verfasserin aut Eva Reininghaus verfasserin aut Guy A. Rouleau verfasserin aut Janusz K. Rybakowski verfasserin aut Martin Schalling verfasserin aut Peter R. Schofield verfasserin aut Barbara W. Schweizer verfasserin aut Giovanni Severino verfasserin aut Paul D. Shilling verfasserin aut Katzutaka Shimoda verfasserin aut Christian Simhandl verfasserin aut Claire M. Slaney verfasserin aut Claudia Pisanu verfasserin aut Alessio Squassina verfasserin aut Thomas Stamm verfasserin aut Pavla Stopkova verfasserin aut Mario Maj verfasserin aut Gustavo Turecki verfasserin aut Eduard Vieta verfasserin aut Julia Veeh verfasserin aut Stephanie H. Witt verfasserin aut Adam Wright verfasserin aut Peter P. Zandi verfasserin aut Philip B. Mitchell verfasserin aut Michael Bauer verfasserin aut Martin Alda verfasserin aut Marcella Rietschel verfasserin aut Francis J. McMahon verfasserin aut Thomas G. Schulze verfasserin aut Jean-Louis Spadoni verfasserin aut Wahid Boukouaci verfasserin aut Jean-Romain Richard verfasserin aut Philippe Le Corvoisier verfasserin aut Caroline Barrau verfasserin aut Jean-François Zagury verfasserin aut Marion Leboyer verfasserin aut Ryad Tamouza verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 12 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:12 https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/article/cd2b00abcda74c64ac98ae9090e72898 kostenfrei https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/toc/2045-2322 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_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 12
allfieldsSound	10.1038/s41598-021-97140-7 doi (DE-627)DOAJ052704718 (DE-599)DOAJcd2b00abcda74c64ac98ae9090e72898 DE-627 ger DE-627 rakwb eng Sigrid Le Clerc verfasserin aut HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response. Medicine R Science Q Laura Lombardi verfasserin aut Bernhard T. Baune verfasserin aut Azmeraw T. Amare verfasserin aut Klaus Oliver Schubert verfasserin aut Liping Hou verfasserin aut Scott R. Clark verfasserin aut Sergi Papiol verfasserin aut Micah Cearns verfasserin aut Urs Heilbronner verfasserin aut Franziska Degenhardt verfasserin aut Fasil Tekola-Ayele verfasserin aut Yi-Hsiang Hsu verfasserin aut Tatyana Shekhtman verfasserin aut Mazda Adli verfasserin aut Nirmala Akula verfasserin aut Kazufumi Akiyama verfasserin aut Raffaella Ardau verfasserin aut Bárbara Arias verfasserin aut Jean-Michel Aubry verfasserin aut Lena Backlund verfasserin aut Abesh Kumar Bhattacharjee verfasserin aut Frank Bellivier verfasserin aut Antonio Benabarre verfasserin aut Susanne Bengesser verfasserin aut Joanna M. Biernacka verfasserin aut Armin Birner verfasserin aut Clara Brichant-Petitjean verfasserin aut Pablo Cervantes verfasserin aut Hsi-Chung Chen verfasserin aut Caterina Chillotti verfasserin aut Sven Cichon verfasserin aut Cristiana Cruceanu verfasserin aut Piotr M. Czerski verfasserin aut Nina Dalkner verfasserin aut Alexandre Dayer verfasserin aut Maria Del Zompo verfasserin aut J. Raymond DePaulo verfasserin aut Bruno Étain verfasserin aut Stephane Jamain verfasserin aut Peter Falkai verfasserin aut Andreas J. Forstner verfasserin aut Louise Frisen verfasserin aut Mark A. Frye verfasserin aut Janice M. Fullerton verfasserin aut Sébastien Gard verfasserin aut Julie S. Garnham verfasserin aut Fernando S. Goes verfasserin aut Maria Grigoroiu-Serbanescu verfasserin aut Paul Grof verfasserin aut Ryota Hashimoto verfasserin aut Joanna Hauser verfasserin aut Stefan Herms verfasserin aut Per Hoffmann verfasserin aut Esther Jiménez verfasserin aut Jean-Pierre Kahn verfasserin aut Layla Kassem verfasserin aut Po-Hsiu Kuo verfasserin aut Tadafumi Kato verfasserin aut John R. Kelsoe verfasserin aut Sarah Kittel-Schneider verfasserin aut Ewa Ferensztajn-Rochowiak verfasserin aut Barbara König verfasserin aut Ichiro Kusumi verfasserin aut Gonzalo Laje verfasserin aut Mikael Landén verfasserin aut Catharina Lavebratt verfasserin aut Susan G. Leckband verfasserin aut Alfonso Tortorella verfasserin aut Mirko Manchia verfasserin aut Lina Martinsson verfasserin aut Michael J. McCarthy verfasserin aut Susan L. McElroy verfasserin aut Francesc Colom verfasserin aut Vincent Millischer verfasserin aut Marina Mitjans verfasserin aut Francis M. Mondimore verfasserin aut Palmiero Monteleone verfasserin aut Caroline M. Nievergelt verfasserin aut Markus M. Nöthen verfasserin aut Tomas Novák verfasserin aut Claire O’Donovan verfasserin aut Norio Ozaki verfasserin aut Urban Ösby verfasserin aut Andrea Pfennig verfasserin aut James B. Potash verfasserin aut Andreas Reif verfasserin aut Eva Reininghaus verfasserin aut Guy A. Rouleau verfasserin aut Janusz K. Rybakowski verfasserin aut Martin Schalling verfasserin aut Peter R. Schofield verfasserin aut Barbara W. Schweizer verfasserin aut Giovanni Severino verfasserin aut Paul D. Shilling verfasserin aut Katzutaka Shimoda verfasserin aut Christian Simhandl verfasserin aut Claire M. Slaney verfasserin aut Claudia Pisanu verfasserin aut Alessio Squassina verfasserin aut Thomas Stamm verfasserin aut Pavla Stopkova verfasserin aut Mario Maj verfasserin aut Gustavo Turecki verfasserin aut Eduard Vieta verfasserin aut Julia Veeh verfasserin aut Stephanie H. Witt verfasserin aut Adam Wright verfasserin aut Peter P. Zandi verfasserin aut Philip B. Mitchell verfasserin aut Michael Bauer verfasserin aut Martin Alda verfasserin aut Marcella Rietschel verfasserin aut Francis J. McMahon verfasserin aut Thomas G. Schulze verfasserin aut Jean-Louis Spadoni verfasserin aut Wahid Boukouaci verfasserin aut Jean-Romain Richard verfasserin aut Philippe Le Corvoisier verfasserin aut Caroline Barrau verfasserin aut Jean-François Zagury verfasserin aut Marion Leboyer verfasserin aut Ryad Tamouza verfasserin aut In Scientific Reports Nature Portfolio, 2011 11(2021), 1, Seite 12 (DE-627)663366712 (DE-600)2615211-3 20452322 nnns volume:11 year:2021 number:1 pages:12 https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/article/cd2b00abcda74c64ac98ae9090e72898 kostenfrei https://doi.org/10.1038/s41598-021-97140-7 kostenfrei https://doaj.org/toc/2045-2322 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_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_381 GBV_ILN_602 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021 1 12
language	English
source	In Scientific Reports 11(2021), 1, Seite 12 volume:11 year:2021 number:1 pages:12
sourceStr	In Scientific Reports 11(2021), 1, Seite 12 volume:11 year:2021 number:1 pages:12
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Science Q
isfreeaccess_bool	true
container_title	Scientific Reports
authorswithroles_txt_mv	Sigrid Le Clerc @@aut@@ Laura Lombardi @@aut@@ Bernhard T. Baune @@aut@@ Azmeraw T. Amare @@aut@@ Klaus Oliver Schubert @@aut@@ Liping Hou @@aut@@ Scott R. Clark @@aut@@ Sergi Papiol @@aut@@ Micah Cearns @@aut@@ Urs Heilbronner @@aut@@ Franziska Degenhardt @@aut@@ Fasil Tekola-Ayele @@aut@@ Yi-Hsiang Hsu @@aut@@ Tatyana Shekhtman @@aut@@ Mazda Adli @@aut@@ Nirmala Akula @@aut@@ Kazufumi Akiyama @@aut@@ Raffaella Ardau @@aut@@ Bárbara Arias @@aut@@ Jean-Michel Aubry @@aut@@ Lena Backlund @@aut@@ Abesh Kumar Bhattacharjee @@aut@@ Frank Bellivier @@aut@@ Antonio Benabarre @@aut@@ Susanne Bengesser @@aut@@ Joanna M. Biernacka @@aut@@ Armin Birner @@aut@@ Clara Brichant-Petitjean @@aut@@ Pablo Cervantes @@aut@@ Hsi-Chung Chen @@aut@@ Caterina Chillotti @@aut@@ Sven Cichon @@aut@@ Cristiana Cruceanu @@aut@@ Piotr M. Czerski @@aut@@ Nina Dalkner @@aut@@ Alexandre Dayer @@aut@@ Maria Del Zompo @@aut@@ J. Raymond DePaulo @@aut@@ Bruno Étain @@aut@@ Stephane Jamain @@aut@@ Peter Falkai @@aut@@ Andreas J. Forstner @@aut@@ Louise Frisen @@aut@@ Mark A. Frye @@aut@@ Janice M. Fullerton @@aut@@ Sébastien Gard @@aut@@ Julie S. Garnham @@aut@@ Fernando S. Goes @@aut@@ Maria Grigoroiu-Serbanescu @@aut@@ Paul Grof @@aut@@ Ryota Hashimoto @@aut@@ Joanna Hauser @@aut@@ Stefan Herms @@aut@@ Per Hoffmann @@aut@@ Esther Jiménez @@aut@@ Jean-Pierre Kahn @@aut@@ Layla Kassem @@aut@@ Po-Hsiu Kuo @@aut@@ Tadafumi Kato @@aut@@ John R. Kelsoe @@aut@@ Sarah Kittel-Schneider @@aut@@ Ewa Ferensztajn-Rochowiak @@aut@@ Barbara König @@aut@@ Ichiro Kusumi @@aut@@ Gonzalo Laje @@aut@@ Mikael Landén @@aut@@ Catharina Lavebratt @@aut@@ Susan G. Leckband @@aut@@ Alfonso Tortorella @@aut@@ Mirko Manchia @@aut@@ Lina Martinsson @@aut@@ Michael J. McCarthy @@aut@@ Susan L. McElroy @@aut@@ Francesc Colom @@aut@@ Vincent Millischer @@aut@@ Marina Mitjans @@aut@@ Francis M. Mondimore @@aut@@ Palmiero Monteleone @@aut@@ Caroline M. Nievergelt @@aut@@ Markus M. Nöthen @@aut@@ Tomas Novák @@aut@@ Claire O’Donovan @@aut@@ Norio Ozaki @@aut@@ Urban Ösby @@aut@@ Andrea Pfennig @@aut@@ James B. Potash @@aut@@ Andreas Reif @@aut@@ Eva Reininghaus @@aut@@ Guy A. Rouleau @@aut@@ Janusz K. Rybakowski @@aut@@ Martin Schalling @@aut@@ Peter R. Schofield @@aut@@ Barbara W. Schweizer @@aut@@ Giovanni Severino @@aut@@ Paul D. Shilling @@aut@@ Katzutaka Shimoda @@aut@@ Christian Simhandl @@aut@@ Claire M. Slaney @@aut@@ Claudia Pisanu @@aut@@ Alessio Squassina @@aut@@ Thomas Stamm @@aut@@ Pavla Stopkova @@aut@@ Mario Maj @@aut@@ Gustavo Turecki @@aut@@ Eduard Vieta @@aut@@ Julia Veeh @@aut@@ Stephanie H. Witt @@aut@@ Adam Wright @@aut@@ Peter P. Zandi @@aut@@ Philip B. Mitchell @@aut@@ Michael Bauer @@aut@@ Martin Alda @@aut@@ Marcella Rietschel @@aut@@ Francis J. McMahon @@aut@@ Thomas G. Schulze @@aut@@ Jean-Louis Spadoni @@aut@@ Wahid Boukouaci @@aut@@ Jean-Romain Richard @@aut@@ Philippe Le Corvoisier @@aut@@ Caroline Barrau @@aut@@ Jean-François Zagury @@aut@@ Marion Leboyer @@aut@@ Ryad Tamouza @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	663366712
id	DOAJ052704718
language_de	englisch
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author	Sigrid Le Clerc
spellingShingle	Sigrid Le Clerc misc Medicine misc R misc Science misc Q HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
authorStr	Sigrid Le Clerc
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issn	20452322
topic_title	HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
topic	misc Medicine misc R misc Science misc Q
topic_unstemmed	misc Medicine misc R misc Science misc Q
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title	HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
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title_full	HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
author_sort	Sigrid Le Clerc
journal	Scientific Reports
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author_browse	Sigrid Le Clerc Laura Lombardi Bernhard T. Baune Azmeraw T. Amare Klaus Oliver Schubert Liping Hou Scott R. Clark Sergi Papiol Micah Cearns Urs Heilbronner Franziska Degenhardt Fasil Tekola-Ayele Yi-Hsiang Hsu Tatyana Shekhtman Mazda Adli Nirmala Akula Kazufumi Akiyama Raffaella Ardau Bárbara Arias Jean-Michel Aubry Lena Backlund Abesh Kumar Bhattacharjee Frank Bellivier Antonio Benabarre Susanne Bengesser Joanna M. Biernacka Armin Birner Clara Brichant-Petitjean Pablo Cervantes Hsi-Chung Chen Caterina Chillotti Sven Cichon Cristiana Cruceanu Piotr M. Czerski Nina Dalkner Alexandre Dayer Maria Del Zompo J. Raymond DePaulo Bruno Étain Stephane Jamain Peter Falkai Andreas J. Forstner Louise Frisen Mark A. Frye Janice M. Fullerton Sébastien Gard Julie S. Garnham Fernando S. Goes Maria Grigoroiu-Serbanescu Paul Grof Ryota Hashimoto Joanna Hauser Stefan Herms Per Hoffmann Esther Jiménez Jean-Pierre Kahn Layla Kassem Po-Hsiu Kuo Tadafumi Kato John R. Kelsoe Sarah Kittel-Schneider Ewa Ferensztajn-Rochowiak Barbara König Ichiro Kusumi Gonzalo Laje Mikael Landén Catharina Lavebratt Susan G. Leckband Alfonso Tortorella Mirko Manchia Lina Martinsson Michael J. McCarthy Susan L. McElroy Francesc Colom Vincent Millischer Marina Mitjans Francis M. Mondimore Palmiero Monteleone Caroline M. Nievergelt Markus M. Nöthen Tomas Novák Claire O’Donovan Norio Ozaki Urban Ösby Andrea Pfennig James B. Potash Andreas Reif Eva Reininghaus Guy A. Rouleau Janusz K. Rybakowski Martin Schalling Peter R. Schofield Barbara W. Schweizer Giovanni Severino Paul D. Shilling Katzutaka Shimoda Christian Simhandl Claire M. Slaney Claudia Pisanu Alessio Squassina Thomas Stamm Pavla Stopkova Mario Maj Gustavo Turecki Eduard Vieta Julia Veeh Stephanie H. Witt Adam Wright Peter P. Zandi Philip B. Mitchell Michael Bauer Martin Alda Marcella Rietschel Francis J. McMahon Thomas G. Schulze Jean-Louis Spadoni Wahid Boukouaci Jean-Romain Richard Philippe Le Corvoisier Caroline Barrau Jean-François Zagury Marion Leboyer Ryad Tamouza
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format_se	Elektronische Aufsätze
author-letter	Sigrid Le Clerc
doi_str_mv	10.1038/s41598-021-97140-7
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title_sort	hla-drb1 and hla-dqb1 genetic diversity modulates response to lithium in bipolar affective disorders
title_auth	HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
abstract	Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
abstractGer	Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
abstract_unstemmed	Abstract Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
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title_short	HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
url	https://doi.org/10.1038/s41598-021-97140-7 https://doaj.org/article/cd2b00abcda74c64ac98ae9090e72898 https://doaj.org/toc/2045-2322
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author2	Laura Lombardi Bernhard T. Baune Azmeraw T. Amare Klaus Oliver Schubert Liping Hou Scott R. Clark Sergi Papiol Micah Cearns Urs Heilbronner Franziska Degenhardt Fasil Tekola-Ayele Yi-Hsiang Hsu Tatyana Shekhtman Mazda Adli Nirmala Akula Kazufumi Akiyama Raffaella Ardau Bárbara Arias Jean-Michel Aubry Lena Backlund Abesh Kumar Bhattacharjee Frank Bellivier Antonio Benabarre Susanne Bengesser Joanna M. Biernacka Armin Birner Clara Brichant-Petitjean Pablo Cervantes Hsi-Chung Chen Caterina Chillotti Sven Cichon Cristiana Cruceanu Piotr M. Czerski Nina Dalkner Alexandre Dayer Maria Del Zompo J. Raymond DePaulo Bruno Étain Stephane Jamain Peter Falkai Andreas J. Forstner Louise Frisen Mark A. Frye Janice M. Fullerton Sébastien Gard Julie S. Garnham Fernando S. Goes Maria Grigoroiu-Serbanescu Paul Grof Ryota Hashimoto Joanna Hauser Stefan Herms Per Hoffmann Esther Jiménez Jean-Pierre Kahn Layla Kassem Po-Hsiu Kuo Tadafumi Kato John R. Kelsoe Sarah Kittel-Schneider Ewa Ferensztajn-Rochowiak Barbara König Ichiro Kusumi Gonzalo Laje Mikael Landén Catharina Lavebratt Susan G. Leckband Alfonso Tortorella Mirko Manchia Lina Martinsson Michael J. McCarthy Susan L. McElroy Francesc Colom Vincent Millischer Marina Mitjans Francis M. Mondimore Palmiero Monteleone Caroline M. Nievergelt Markus M. Nöthen Tomas Novák Claire O’Donovan Norio Ozaki Urban Ösby Andrea Pfennig James B. Potash Andreas Reif Eva Reininghaus Guy A. Rouleau Janusz K. Rybakowski Martin Schalling Peter R. Schofield Barbara W. Schweizer Giovanni Severino Paul D. Shilling Katzutaka Shimoda Christian Simhandl Claire M. Slaney Claudia Pisanu Alessio Squassina Thomas Stamm Pavla Stopkova Mario Maj Gustavo Turecki Eduard Vieta Julia Veeh Stephanie H. Witt Adam Wright Peter P. Zandi Philip B. Mitchell Michael Bauer Martin Alda Marcella Rietschel Francis J. McMahon Thomas G. Schulze Jean-Louis Spadoni Wahid Boukouaci Jean-Romain Richard Philippe Le Corvoisier Caroline Barrau Jean-François Zagury Marion Leboyer Ryad Tamouza
author2Str	Laura Lombardi Bernhard T. Baune Azmeraw T. Amare Klaus Oliver Schubert Liping Hou Scott R. Clark Sergi Papiol Micah Cearns Urs Heilbronner Franziska Degenhardt Fasil Tekola-Ayele Yi-Hsiang Hsu Tatyana Shekhtman Mazda Adli Nirmala Akula Kazufumi Akiyama Raffaella Ardau Bárbara Arias Jean-Michel Aubry Lena Backlund Abesh Kumar Bhattacharjee Frank Bellivier Antonio Benabarre Susanne Bengesser Joanna M. Biernacka Armin Birner Clara Brichant-Petitjean Pablo Cervantes Hsi-Chung Chen Caterina Chillotti Sven Cichon Cristiana Cruceanu Piotr M. Czerski Nina Dalkner Alexandre Dayer Maria Del Zompo J. Raymond DePaulo Bruno Étain Stephane Jamain Peter Falkai Andreas J. Forstner Louise Frisen Mark A. Frye Janice M. Fullerton Sébastien Gard Julie S. Garnham Fernando S. Goes Maria Grigoroiu-Serbanescu Paul Grof Ryota Hashimoto Joanna Hauser Stefan Herms Per Hoffmann Esther Jiménez Jean-Pierre Kahn Layla Kassem Po-Hsiu Kuo Tadafumi Kato John R. Kelsoe Sarah Kittel-Schneider Ewa Ferensztajn-Rochowiak Barbara König Ichiro Kusumi Gonzalo Laje Mikael Landén Catharina Lavebratt Susan G. Leckband Alfonso Tortorella Mirko Manchia Lina Martinsson Michael J. McCarthy Susan L. McElroy Francesc Colom Vincent Millischer Marina Mitjans Francis M. Mondimore Palmiero Monteleone Caroline M. Nievergelt Markus M. Nöthen Tomas Novák Claire O’Donovan Norio Ozaki Urban Ösby Andrea Pfennig James B. Potash Andreas Reif Eva Reininghaus Guy A. Rouleau Janusz K. Rybakowski Martin Schalling Peter R. Schofield Barbara W. Schweizer Giovanni Severino Paul D. Shilling Katzutaka Shimoda Christian Simhandl Claire M. Slaney Claudia Pisanu Alessio Squassina Thomas Stamm Pavla Stopkova Mario Maj Gustavo Turecki Eduard Vieta Julia Veeh Stephanie H. Witt Adam Wright Peter P. Zandi Philip B. Mitchell Michael Bauer Martin Alda Marcella Rietschel Francis J. McMahon Thomas G. Schulze Jean-Louis Spadoni Wahid Boukouaci Jean-Romain Richard Philippe Le Corvoisier Caroline Barrau Jean-François Zagury Marion Leboyer Ryad Tamouza
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up_date	2024-07-03T13:35:34.357Z
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