Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
| Autor: | Patrick Mathieu, Tõnu Esko, Émilie Gobeil, Erik Abner, Nele Taba, Christian Couture, Yohan Bossé, Amit Khera, Nicolas Perrot, Benoit J. Arsenault, Connor A. Emdin, Éloi Gagnon, Jérôme Bourgault, Nooshin Ghodsian, Mary E. Haas, Hasanga D. Manikpurage, Marie-Claude Vohl, Patricia L. Mitchell, Sébastien Thériault, André Tchernof, Alexis St-Amand |
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| Rok vydání: | 2021 |
| Předmět: |
Apolipoprotein E
Medicine (General) lipoprotein lipase Genome-wide association study Disease Bioinformatics digestive system Article Linkage Disequilibrium General Biochemistry Genetics and Molecular Biology R5-920 Insulin resistance Genotype medicine Humans genetics Genetic Predisposition to Disease Obesity genome-wide association study business.industry Fatty liver non-alcoholic fatty liver disease Genetic Variation nutritional and metabolic diseases medicine.disease digestive system diseases Genetic architecture adipose tissue electronic health records Phenotype business TM6SF2 |
| Zdroj: | Cell Reports Medicine Cell Reports Medicine, Vol 2, Iss 11, Pp 100437-(2021) |
| ISSN: | 2666-3791 |
| Popis: | 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. Graphical abstract Highlights This analysis identifies 5 genetic loci for non-alcoholic fatty liver disease Non-alcoholic fatty liver disease loci are GCKR, TR1B1, TM6SF2, APOE, and PNPLA3 Adipose tissue LPL expression may influence non-alcoholic fatty liver disease The 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). |
| Databáze: | OpenAIRE |
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