Cell reports. Medicine · 2021
Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease.
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Ghodsian Nooshin, Abner Erik, Emdin Connor A, Gobeil Émilie, Taba Nele, Haas Mary E, Perrot Nicolas, Manikpurage Hasanga D, Gagnon Éloi, Bourgault Jérôme, St-Amand Alexis, Couture Christian, Mitchell Patricia L, Bossé Yohan, Mathieu Patrick, Vohl Marie-Claude, Tchernof André, Thériault Sébastien, Khera Amit V, Esko Tõnu, Arsenault Benoit J
Аннотация
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.