Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease

Summary: Non-alcoholic fatty liver disease (NAFLD) is a complex disease linked to several chronic diseases. We aimed at identifying genetic variants associated with NAFLD and evaluating their functional consequences. We performed a genome-wide meta-analysis of 4 cohorts of electronic health record-d...

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Autores principales:	Nooshin Ghodsian, Erik Abner, Connor A. Emdin, Émilie Gobeil, Nele Taba, Mary E. Haas, Nicolas Perrot, Hasanga D. Manikpurage, Éloi Gagnon, Jérôme Bourgault, Alexis St-Amand, Christian Couture, Patricia L. Mitchell, Yohan Bossé, Patrick Mathieu, Marie-Claude Vohl, André Tchernof, Sébastien Thériault, Amit V. Khera, Tõnu Esko, Benoit J. Arsenault
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	genetics non-alcoholic fatty liver disease genome-wide association study electronic health records adipose tissue lipoprotein lipase Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/19e306941a06424da1e769a90f8e839d
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spelling	oai:doaj.org-article:19e306941a06424da1e769a90f8e839d2021-11-18T04:52:11ZElectronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease2666-379110.1016/j.xcrm.2021.100437https://doaj.org/article/19e306941a06424da1e769a90f8e839d2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666379121002998https://doaj.org/toc/2666-3791Summary: Non-alcoholic fatty liver disease (NAFLD) is a complex disease linked to several chronic diseases. We aimed at identifying genetic variants associated with NAFLD and evaluating their functional consequences. We performed a genome-wide meta-analysis of 4 cohorts of electronic health record-documented NAFLD in participants of European ancestry (8,434 cases and 770,180 controls). We identify 5 potential susceptibility loci for NAFLD (located at or near GCKR, TR1B1, MAU2/TM6SF2, APOE, and PNPLA3). We also report a potentially causal effect of lower LPL expression in adipose tissue on NAFLD susceptibility and an effect of the FTO genotype on NAFLD. Positive genetic correlations between NAFLD and cardiometabolic diseases and risk factors such as body fat accumulation/distribution, lipoprotein-lipid levels, insulin resistance, and coronary artery disease and negative genetic correlations with parental lifespan, socio-economic status, and acetoacetate levels are observed. This large GWAS meta-analysis reveals insights into the genetic architecture of NAFLD.Nooshin GhodsianErik AbnerConnor A. EmdinÉmilie GobeilNele TabaMary E. HaasNicolas PerrotHasanga D. ManikpurageÉloi GagnonJérôme BourgaultAlexis St-AmandChristian CouturePatricia L. MitchellYohan BosséPatrick MathieuMarie-Claude VohlAndré TchernofSébastien ThériaultAmit V. KheraTõnu EskoBenoit J. ArsenaultElsevierarticlegeneticsnon-alcoholic fatty liver diseasegenome-wide association studyelectronic health recordsadipose tissuelipoprotein lipaseMedicine (General)R5-920ENCell Reports Medicine, Vol 2, Iss 11, Pp 100437- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	genetics non-alcoholic fatty liver disease genome-wide association study electronic health records adipose tissue lipoprotein lipase Medicine (General) R5-920
spellingShingle	genetics non-alcoholic fatty liver disease genome-wide association study electronic health records adipose tissue lipoprotein lipase Medicine (General) R5-920 Nooshin Ghodsian Erik Abner Connor A. Emdin Émilie Gobeil Nele Taba Mary E. Haas Nicolas Perrot Hasanga D. Manikpurage Éloi Gagnon Jérôme Bourgault Alexis St-Amand Christian Couture Patricia L. Mitchell Yohan Bossé Patrick Mathieu Marie-Claude Vohl André Tchernof Sébastien Thériault Amit V. Khera Tõnu Esko Benoit J. Arsenault Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
description	Summary: Non-alcoholic fatty liver disease (NAFLD) is a complex disease linked to several chronic diseases. We aimed at identifying genetic variants associated with NAFLD and evaluating their functional consequences. We performed a genome-wide meta-analysis of 4 cohorts of electronic health record-documented NAFLD in participants of European ancestry (8,434 cases and 770,180 controls). We identify 5 potential susceptibility loci for NAFLD (located at or near GCKR, TR1B1, MAU2/TM6SF2, APOE, and PNPLA3). We also report a potentially causal effect of lower LPL expression in adipose tissue on NAFLD susceptibility and an effect of the FTO genotype on NAFLD. Positive genetic correlations between NAFLD and cardiometabolic diseases and risk factors such as body fat accumulation/distribution, lipoprotein-lipid levels, insulin resistance, and coronary artery disease and negative genetic correlations with parental lifespan, socio-economic status, and acetoacetate levels are observed. This large GWAS meta-analysis reveals insights into the genetic architecture of NAFLD.
format	article
author	Nooshin Ghodsian Erik Abner Connor A. Emdin Émilie Gobeil Nele Taba Mary E. Haas Nicolas Perrot Hasanga D. Manikpurage Éloi Gagnon Jérôme Bourgault Alexis St-Amand Christian Couture Patricia L. Mitchell Yohan Bossé Patrick Mathieu Marie-Claude Vohl André Tchernof Sébastien Thériault Amit V. Khera Tõnu Esko Benoit J. Arsenault
author_facet	Nooshin Ghodsian Erik Abner Connor A. Emdin Émilie Gobeil Nele Taba Mary E. Haas Nicolas Perrot Hasanga D. Manikpurage Éloi Gagnon Jérôme Bourgault Alexis St-Amand Christian Couture Patricia L. Mitchell Yohan Bossé Patrick Mathieu Marie-Claude Vohl André Tchernof Sébastien Thériault Amit V. Khera Tõnu Esko Benoit J. Arsenault
author_sort	Nooshin Ghodsian
title	Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
title_short	Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
title_full	Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
title_fullStr	Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
title_full_unstemmed	Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
title_sort	electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/19e306941a06424da1e769a90f8e839d
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Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease

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