Nature communications · 2019
Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Kranzler Henry R, Zhou Hang, Kember Rachel L, Vickers Smith Rachel, Justice Amy C, Damrauer Scott, Tsao Philip S, Klarin Derek, Baras Aris, Reid Jeffrey, Overton John, Rader Daniel J, Cheng Zhongshan, Tate Janet P, Becker William C, Concato John, Xu Ke, Polimanti Renato, Zhao Hongyu, Gelernter Joel
Аннотация
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.