Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease.
meta_analysis · Level I
Where this comes from
- Record sourced from PubMed, PMID 34841290.
- Also identified by DOI 10.1016/j.xcrm.2021.100437 and PMC identifier 8606899.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>GCKR</i>, <i>TR1B1</i>, <i>MAU2</i>/<i>TM6SF2</i>, <i>APOE</i>, and <i>PNPLA3</i>). We also report a potentially causal effect of lower <i>LPL</i> expression in adipose tissue on NAFLD susceptibility and an effect of the <i>FTO</i> 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.
Medical subject headings
- Electronic Health Records
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Non-alcoholic Fatty Liver Disease