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

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, Zhongshan Cheng, Janet P. Tate, William C. Becker, John Concato, Ke Xu, Renato Polimanti, Hongyu Zhao, Joel Gelernter

Research output: Contribution to journalArticlepeer-review

340 Scopus citations

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.

Original languageEnglish
Article number1499
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Publisher Copyright:
© 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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