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

• Published in: Cell reports. Medicine Vol. 2; no. 11; p. 100437
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.11.2021; Elsevier
• Subjects: adipose tissue; Electronic Health Records; Genetic Predisposition to Disease; Genetic Variation; genetics; Genome-Wide Association Study; Humans; Linkage Disequilibrium - genetics; lipoprotein lipase; Lipoprotein Lipase - genetics; non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - genetics; Obesity - genetics; Phenotype; adipose tissue; genetics; non-alcoholic fatty liver disease; electronic health records; lipoprotein lipase; genome-wide association study
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2021.100437

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. [Display omitted] This analysis identifies 5 genetic loci for non-alcoholic fatty liver diseaseNon-alcoholic fatty liver disease loci are GCKR, TR1B1, TM6SF2, APOE, and PNPLA3Adipose tissue LPL expression may influence non-alcoholic fatty liver diseaseThe FTO genotype may affect non-alcoholic fatty liver disease susceptibility To gain insight into the genetic architecture of non-alcoholic fatty liver disease (NAFLD), Ghodsian et al. performed a genome-wide meta-analysis of electronic health record-documented NAFLD and identify 7 potential susceptibility loci for this disease (located at or near GCKR, TR1B1, LPL, FTO, MAU2/TM6SF2, APOE, and PNPLA3).