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Nat Commun. 2019 Apr 2;10(1):1499. doi: 10.1038/s41467-019-09480-8.

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

Author information

1
University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. kranzler@pennmedicine.upenn.edu.
2
Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA. kranzler@pennmedicine.upenn.edu.
3
Yale School of Medicine, New Haven, CT, 06511, USA.
4
Veterans Affairs Connecticut Healthcare System, West Haven, CT, 06516, USA.
5
University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
6
Crescenz Veterans Affairs Medical Center, Philadelphia, PA, 19104, USA.
7
University of Louisville School of Nursing, Louisville, KY, 40202, USA.
8
Yale School of Public Health, New Haven, CT, 06511, USA.
9
VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
10
Stanford University School of Medicine, Stanford, CA, 94305, USA.
11
Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
12
Regeneron Genetics Center, Tarrytown, NY, 10591, USA.

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.

PMID:
30940813
PMCID:
PMC6445072
DOI:
10.1038/s41467-019-09480-8
[Indexed for MEDLINE]
Free PMC Article

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