Authors
Hang Zhou, Julia M Sealock, Sandra Sanchez-Roige, Toni-Kim Clarke, Daniel F Levey, Zhongshan Cheng, Boyang Li, Renato Polimanti, Rachel L Kember, Rachel Vickers Smith, Johan H Thygesen, Marsha Y Morgan, Stephen R Atkinson, Mark R Thursz, Mette Nyegaard, Manuel Mattheisen, Anders D Børglum, Emma C Johnson, Amy C Justice, Abraham A Palmer, Andrew McQuillin, Lea K Davis, Howard J Edenberg, Arpana Agrawal, Henry R Kranzler, Joel Gelernter
Publication date
2020/7
Journal
Nature neuroscience
Volume
23
Issue
7
Pages
809-818
Publisher
Nature Publishing Group US
Description
Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU, combining alcohol use disorder and problematic drinking, in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n = 67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in conserved and regulatory genomic regions. Mendelian randomization suggested causal effects on liability to PAU of …
Scholar articles
H Zhou, JM Sealock, S Sanchez-Roige, TK Clarke… - Nature neuroscience, 2020