Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology.

There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used...
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Autor*in:	Laurence J Howe [verfasserIn] Myoung Keun Lee [verfasserIn] Gemma C Sharp [verfasserIn] George Davey Smith [verfasserIn] Beate St Pourcain [verfasserIn] John R Shaffer [verfasserIn] Kerstin U Ludwig [verfasserIn] Elisabeth Mangold [verfasserIn] Mary L Marazita [verfasserIn] Eleanor Feingold [verfasserIn] Alexei Zhurov [verfasserIn] Evie Stergiakouli [verfasserIn] Jonathan Sandy [verfasserIn] Stephen Richmond [verfasserIn] Seth M Weinberg [verfasserIn] Gibran Hemani [verfasserIn] Sarah J Lewis [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Übergeordnetes Werk:	In: PLoS Genetics - Public Library of Science (PLoS), 2005, 14(2018), 8, p e1007501
Übergeordnetes Werk:	volume:14 ; year:2018 ; number:8, p e1007501

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1371/journal.pgen.1007501

Katalog-ID:	DOAJ052158721

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520			\|a There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum.
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allfields	10.1371/journal.pgen.1007501 doi (DE-627)DOAJ052158721 (DE-599)DOAJfce4f3a95f2a43b4beeacd55bb4e7ff5 DE-627 ger DE-627 rakwb eng QH426-470 Laurence J Howe verfasserin aut Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum. Genetics Myoung Keun Lee verfasserin aut Gemma C Sharp verfasserin aut George Davey Smith verfasserin aut Beate St Pourcain verfasserin aut John R Shaffer verfasserin aut Kerstin U Ludwig verfasserin aut Elisabeth Mangold verfasserin aut Mary L Marazita verfasserin aut Eleanor Feingold verfasserin aut Alexei Zhurov verfasserin aut Evie Stergiakouli verfasserin aut Jonathan Sandy verfasserin aut Stephen Richmond verfasserin aut Seth M Weinberg verfasserin aut Gibran Hemani verfasserin aut Sarah J Lewis verfasserin aut In PLoS Genetics Public Library of Science (PLoS), 2005 14(2018), 8, p e1007501 (DE-627)485248026 (DE-600)2186725-2 15537404 nnns volume:14 year:2018 number:8, p e1007501 https://doi.org/10.1371/journal.pgen.1007501 kostenfrei https://doaj.org/article/fce4f3a95f2a43b4beeacd55bb4e7ff5 kostenfrei http://europepmc.org/articles/PMC6089455?pdf=render kostenfrei https://doaj.org/toc/1553-7390 Journal toc kostenfrei https://doaj.org/toc/1553-7404 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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 14 2018 8, p e1007501
spelling	10.1371/journal.pgen.1007501 doi (DE-627)DOAJ052158721 (DE-599)DOAJfce4f3a95f2a43b4beeacd55bb4e7ff5 DE-627 ger DE-627 rakwb eng QH426-470 Laurence J Howe verfasserin aut Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum. Genetics Myoung Keun Lee verfasserin aut Gemma C Sharp verfasserin aut George Davey Smith verfasserin aut Beate St Pourcain verfasserin aut John R Shaffer verfasserin aut Kerstin U Ludwig verfasserin aut Elisabeth Mangold verfasserin aut Mary L Marazita verfasserin aut Eleanor Feingold verfasserin aut Alexei Zhurov verfasserin aut Evie Stergiakouli verfasserin aut Jonathan Sandy verfasserin aut Stephen Richmond verfasserin aut Seth M Weinberg verfasserin aut Gibran Hemani verfasserin aut Sarah J Lewis verfasserin aut In PLoS Genetics Public Library of Science (PLoS), 2005 14(2018), 8, p e1007501 (DE-627)485248026 (DE-600)2186725-2 15537404 nnns volume:14 year:2018 number:8, p e1007501 https://doi.org/10.1371/journal.pgen.1007501 kostenfrei https://doaj.org/article/fce4f3a95f2a43b4beeacd55bb4e7ff5 kostenfrei http://europepmc.org/articles/PMC6089455?pdf=render kostenfrei https://doaj.org/toc/1553-7390 Journal toc kostenfrei https://doaj.org/toc/1553-7404 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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 14 2018 8, p e1007501
allfields_unstemmed	10.1371/journal.pgen.1007501 doi (DE-627)DOAJ052158721 (DE-599)DOAJfce4f3a95f2a43b4beeacd55bb4e7ff5 DE-627 ger DE-627 rakwb eng QH426-470 Laurence J Howe verfasserin aut Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum. Genetics Myoung Keun Lee verfasserin aut Gemma C Sharp verfasserin aut George Davey Smith verfasserin aut Beate St Pourcain verfasserin aut John R Shaffer verfasserin aut Kerstin U Ludwig verfasserin aut Elisabeth Mangold verfasserin aut Mary L Marazita verfasserin aut Eleanor Feingold verfasserin aut Alexei Zhurov verfasserin aut Evie Stergiakouli verfasserin aut Jonathan Sandy verfasserin aut Stephen Richmond verfasserin aut Seth M Weinberg verfasserin aut Gibran Hemani verfasserin aut Sarah J Lewis verfasserin aut In PLoS Genetics Public Library of Science (PLoS), 2005 14(2018), 8, p e1007501 (DE-627)485248026 (DE-600)2186725-2 15537404 nnns volume:14 year:2018 number:8, p e1007501 https://doi.org/10.1371/journal.pgen.1007501 kostenfrei https://doaj.org/article/fce4f3a95f2a43b4beeacd55bb4e7ff5 kostenfrei http://europepmc.org/articles/PMC6089455?pdf=render kostenfrei https://doaj.org/toc/1553-7390 Journal toc kostenfrei https://doaj.org/toc/1553-7404 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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 14 2018 8, p e1007501
allfieldsGer	10.1371/journal.pgen.1007501 doi (DE-627)DOAJ052158721 (DE-599)DOAJfce4f3a95f2a43b4beeacd55bb4e7ff5 DE-627 ger DE-627 rakwb eng QH426-470 Laurence J Howe verfasserin aut Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum. Genetics Myoung Keun Lee verfasserin aut Gemma C Sharp verfasserin aut George Davey Smith verfasserin aut Beate St Pourcain verfasserin aut John R Shaffer verfasserin aut Kerstin U Ludwig verfasserin aut Elisabeth Mangold verfasserin aut Mary L Marazita verfasserin aut Eleanor Feingold verfasserin aut Alexei Zhurov verfasserin aut Evie Stergiakouli verfasserin aut Jonathan Sandy verfasserin aut Stephen Richmond verfasserin aut Seth M Weinberg verfasserin aut Gibran Hemani verfasserin aut Sarah J Lewis verfasserin aut In PLoS Genetics Public Library of Science (PLoS), 2005 14(2018), 8, p e1007501 (DE-627)485248026 (DE-600)2186725-2 15537404 nnns volume:14 year:2018 number:8, p e1007501 https://doi.org/10.1371/journal.pgen.1007501 kostenfrei https://doaj.org/article/fce4f3a95f2a43b4beeacd55bb4e7ff5 kostenfrei http://europepmc.org/articles/PMC6089455?pdf=render kostenfrei https://doaj.org/toc/1553-7390 Journal toc kostenfrei https://doaj.org/toc/1553-7404 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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 14 2018 8, p e1007501
allfieldsSound	10.1371/journal.pgen.1007501 doi (DE-627)DOAJ052158721 (DE-599)DOAJfce4f3a95f2a43b4beeacd55bb4e7ff5 DE-627 ger DE-627 rakwb eng QH426-470 Laurence J Howe verfasserin aut Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology. 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum. Genetics Myoung Keun Lee verfasserin aut Gemma C Sharp verfasserin aut George Davey Smith verfasserin aut Beate St Pourcain verfasserin aut John R Shaffer verfasserin aut Kerstin U Ludwig verfasserin aut Elisabeth Mangold verfasserin aut Mary L Marazita verfasserin aut Eleanor Feingold verfasserin aut Alexei Zhurov verfasserin aut Evie Stergiakouli verfasserin aut Jonathan Sandy verfasserin aut Stephen Richmond verfasserin aut Seth M Weinberg verfasserin aut Gibran Hemani verfasserin aut Sarah J Lewis verfasserin aut In PLoS Genetics Public Library of Science (PLoS), 2005 14(2018), 8, p e1007501 (DE-627)485248026 (DE-600)2186725-2 15537404 nnns volume:14 year:2018 number:8, p e1007501 https://doi.org/10.1371/journal.pgen.1007501 kostenfrei https://doaj.org/article/fce4f3a95f2a43b4beeacd55bb4e7ff5 kostenfrei http://europepmc.org/articles/PMC6089455?pdf=render kostenfrei https://doaj.org/toc/1553-7390 Journal toc kostenfrei https://doaj.org/toc/1553-7404 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 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 14 2018 8, p e1007501
language	English
source	In PLoS Genetics 14(2018), 8, p e1007501 volume:14 year:2018 number:8, p e1007501
sourceStr	In PLoS Genetics 14(2018), 8, p e1007501 volume:14 year:2018 number:8, p e1007501
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Genetics
isfreeaccess_bool	true
container_title	PLoS Genetics
authorswithroles_txt_mv	Laurence J Howe @@aut@@ Myoung Keun Lee @@aut@@ Gemma C Sharp @@aut@@ George Davey Smith @@aut@@ Beate St Pourcain @@aut@@ John R Shaffer @@aut@@ Kerstin U Ludwig @@aut@@ Elisabeth Mangold @@aut@@ Mary L Marazita @@aut@@ Eleanor Feingold @@aut@@ Alexei Zhurov @@aut@@ Evie Stergiakouli @@aut@@ Jonathan Sandy @@aut@@ Stephen Richmond @@aut@@ Seth M Weinberg @@aut@@ Gibran Hemani @@aut@@ Sarah J Lewis @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	485248026
id	DOAJ052158721
language_de	englisch
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callnumber-first	Q - Science
author	Laurence J Howe
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topic_title	QH426-470 Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology
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title	Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology.
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title_full	Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology
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title_sort	investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology
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title_auth	Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology.
abstract	There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum.
abstractGer	There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum.
abstract_unstemmed	There is increasing evidence that genetic risk variants for non-syndromic cleft lip/palate (nsCL/P) are also associated with normal-range variation in facial morphology. However, previous analyses are mostly limited to candidate SNPs and findings have not been consistently replicated. Here, we used polygenic risk scores (PRS) to test for genetic overlap between nsCL/P and seven biologically relevant facial phenotypes. Where evidence was found of genetic overlap, we used bidirectional Mendelian randomization (MR) to test the hypothesis that genetic liability to nsCL/P is causally related to implicated facial phenotypes. Across 5,804 individuals of European ancestry from two studies, we found strong evidence, using PRS, of genetic overlap between nsCL/P and philtrum width; a 1 S.D. increase in nsCL/P PRS was associated with a 0.10 mm decrease in philtrum width (95% C.I. 0.054, 0.146; P = 2x10-5). Follow-up MR analyses supported a causal relationship; genetic variants for nsCL/P homogeneously cause decreased philtrum width. In addition to the primary analysis, we also identified two novel risk loci for philtrum width at 5q22.2 and 7p15.2 in our Genome-wide Association Study (GWAS) of 6,136 individuals. Our results support a liability threshold model of inheritance for nsCL/P, related to abnormalities in development of the philtrum.
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title_short	Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology.
url	https://doi.org/10.1371/journal.pgen.1007501 https://doaj.org/article/fce4f3a95f2a43b4beeacd55bb4e7ff5 http://europepmc.org/articles/PMC6089455?pdf=render https://doaj.org/toc/1553-7390 https://doaj.org/toc/1553-7404
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Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology.

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