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

Abstract

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.

• Authors: 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
• Journal: Cell reports. Medicine (Cell Rep Med) Vol. 2 Issue 11 Pg. 100437 (11 16 2021) ISSN: 2666-3791 [Electronic] United States
• PMID: 34841290 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Author(s).

Chemical References

• Lipoprotein Lipase

Topics

• Electronic Health Records
• Genetic Predisposition to Disease
• Genetic Variation
• Genome-Wide Association Study
• Humans
• Linkage Disequilibrium (genetics)
• Lipoprotein Lipase (genetics)
• Non-alcoholic Fatty Liver Disease (genetics)
• Obesity (genetics)
• Phenotype