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Publication Detail
Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Zhou H, Sealock JM, Sanchez-Roige S, Clarke T-K, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J
  • Publisher:
    Nature Publishing Group
  • Publication date:
    01/07/2020
  • Journal:
    Nature Neuroscience
  • Status:
    Published
  • Country:
    United States
  • Print ISSN:
    1097-6256
  • PII:
    10.1038/s41593-020-0643-5
  • Language:
    eng
Abstract
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 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 traits.
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