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

Author

Listed:
  • Henry R. Kranzler

    (University of Pennsylvania Perelman School of Medicine
    Crescenz Veterans Affairs Medical Center)

  • Hang Zhou

    (Yale School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • Rachel L. Kember

    (University of Pennsylvania Perelman School of Medicine
    Crescenz Veterans Affairs Medical Center)

  • Rachel Vickers Smith

    (Crescenz Veterans Affairs Medical Center
    University of Louisville School of Nursing)

  • Amy C. Justice

    (Yale School of Medicine
    Veterans Affairs Connecticut Healthcare System
    Yale School of Public Health)

  • Scott Damrauer

    (University of Pennsylvania Perelman School of Medicine
    Crescenz Veterans Affairs Medical Center)

  • Philip S. Tsao

    (VA Palo Alto Health Care System
    Stanford University School of Medicine)

  • Derek Klarin

    (Harvard Medical School)

  • Aris Baras

    (Regeneron Genetics Center)

  • Jeffrey Reid

    (Regeneron Genetics Center)

  • John Overton

    (Regeneron Genetics Center)

  • Daniel J. Rader

    (University of Pennsylvania Perelman School of Medicine)

  • Zhongshan Cheng

    (Yale School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • Janet P. Tate

    (Yale School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • William C. Becker

    (Yale School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • John Concato

    (Yale School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • Ke Xu

    (Yale School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • Renato Polimanti

    (Yale School of Medicine
    Veterans Affairs Connecticut Healthcare System)

  • Hongyu Zhao

    (Yale School of Medicine
    Yale School of Public Health)

  • Joel Gelernter

    (Yale School of Medicine
    Veterans Affairs Connecticut Healthcare System)

Abstract

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.

Suggested Citation

  • Henry R. Kranzler & Hang Zhou & Rachel L. Kember & Rachel Vickers Smith & Amy C. Justice & Scott Damrauer & Philip S. Tsao & Derek Klarin & Aris Baras & Jeffrey Reid & John Overton & Daniel J. Rader &, 2019. "Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09480-8
    DOI: 10.1038/s41467-019-09480-8
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