Meta-analysis of problematic alcohol use in 435,563 individuals identifies 29 risk variants and yields insights into biology, pleiotropy and causality

作者: Hang Zhou , Julia M. Sealock , Sandra Sanchez-Roige , Toni-Kim Clarke , Daniel Levey

DOI: 10.1101/738088

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摘要: Abstract Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies (GWASs) have identified PAU risk genes, the genetic architecture this trait not fully understood. We conducted proxy-phenotype meta-analysis combining disorder problematic drinking in 435,563 European-ancestry individuals. 29 independent variants, 19 them novel. was genetically correlated with 138 phenotypes, including substance psychiatric traits. Phenome-wide polygenic score analysis an biobank sample (BioVU, n=67,589) confirmed correlations between disorders. Genetic heritability enriched brain genomic conserved regulatory regions. Mendelian randomization suggested causal effects on liability to use, status, risk-taking behavior, cognitive performance. In summary, large novel loci revealed relationships numerous other outcomes.

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