Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits
Year: 2020
Type: review
Study design: Observational Study
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 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 genomic conserved and regulatory regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior, and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other outcomes.
Source: Nature Neuroscience
Authors: Hang Zhou, Julia M. Sealock, Sandra Sanchez-Roige, Toni-Kim Clarke, Daniel 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, the VA Million Veteran Program, Amy C. Justice, Abraham A. Palmer, Andrew McQuillin, Lea K. Davis, Howard J. Edenberg, Arpana Agrawal, Henry R. Kranzler, Joel Gelernter
Institutions: Yale University, VA Connecticut Healthcare System, Vanderbilt University, Vanderbilt University Medical Center, University of California San Diego, University of Edinburgh, Philadelphia VA Medical Center, University of Pennsylvania, University of Louisville, University College London, The Royal Free Hospital, Imperial College London, Aarhus University, Lundbeck Foundation, University of Würzburg, Karolinska Institutet, Washington University in St. Louis, Indiana University Indianapolis, Indiana University School of Medicine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Health and Human Services, U.S. Department of Veterans Affairs, Brain and Behavior Research Foundation, Eli Lilly and Company, Pfizer, Office of Research and Development, Aarhus Universitet, National Alliance for Research on Schizophrenia and Depression, University of Essex, Wellcome Trust, Indivior, Understanding Society, American Society of Clinical Psychopharmacology, National Institute for Health and Care Research, University College London, Lundbeckfonden, Novo Nordisk, University College London Hospitals NHS Foundation Trust, Novo Nordisk Fonden, H. Lundbeck A/S, National Institutes of Health, Medical Research Council, Economic and Social Research Council, NIHR Imperial Biomedical Research Centre, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Center for Advancing Translational Sciences
Awards: G1044130170, G1083756078, G1128022803, G1250591687, G1309605592, G1371274626, Center for the Translational Neuroscience of Alcoholism, Training Program on Genetic Variation and Human Phenotypes, G1482489452, G152221931, 5/7 Psychiatric Genomics Consortium: Finding actionable variation, G1853051483, G214445032, G2402392985, G2435409293, G2467602100, G2628014196, G2719215791, G2743192107, G2818438833, G2905247291, G2924140200, G2988863959, G3051910871, G3232631211, G3240712639, G3246699782, G4102788581, G4193739534, G4468564356, G4944172205, G5069484653, G511006989, G5442465175, G5520109959, G6043135521, G6386703888, G6467827404, G653240219, DELINEATING THE ROLE OF GENETIC INFLUENCES ON CANNABIS INVOLVEMENT, G6988814273, G7005625235, 7/7 Psychiatric Genomics Consortium: Finding actionable variation, G8160215347, Modular Automated -80C Sample Storage System, G9000006508, G9000013469, G9000145302, G9000246251, G9000281634
OpenAlex ID: W3026319555