Journal Article

Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations

Becker, William C., Reid, Jeffrey, Tsao, Philip S., Xu, Ke, Justice, Amy C., Cheng, Zhongshan, Zhao, Hongyu, Damrauer, Scott, Rader, Daniel J., Baras, Aris, Zhou, Hang, Vickers Smith, Rachel, Klarin, Derek, Overton, John, Kranzler, Henry R., Tate, Janet P., Polimanti, Renato, Gelernter, Joel, Concato, John, Kember, Rachel L.

2019

Overview

Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample ( N  = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits’ PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder. The genetic underpinnings of alcohol use disorder and consumption are incompletely understood. Here, the authors perform GWAS for Alcohol Use Disorder (AUD) Identification Test-Consumption scores and AUD diagnosis from electronic health records of 274,424 individuals and identify a total of 18 associated loci.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45 / 45/43 / 631/208/205/2138 / 692/308/2056 / 692/699/476/5 / 692/700/478/174 / Adult / Aged / Aged, 80 and over / Alcohol Drinking - genetics / Alcohol use / Alcoholic beverages / Alcoholism - genetics / Alcohols / Diagnosis / Drinking behavior / Female / Genome-wide association studies / Genome-Wide Association Study / Genomes / Heritability / Humanities and Social Sciences / Humans / Longitudinal Studies / Male / Middle Aged / multidisciplinary / Multifactorial Inheritance / Phenotype / Phenotypes / Polygenic inheritance / Polymorphism, Single Nucleotide / Risk analysis / Risk factors / Science / Science (multidisciplinary) / Young Adult