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 language | English |
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Article number | 1499 |
Journal | Nature Communications |
Volume | 10 |
Issue number | 1 |
DOIs | |
State | Published - Dec 1 2019 |
Bibliographical note
Funding Information:This research is based on data from the Million Veteran Program (MVP), Office of Research and Development, Veterans Health Administration, and was supported by award #I01BX003341. This publication does not represent the views of the Department of Veterans Affairs or the United States Government. A full acknowledgment of the MVP is included in Supplementary Note 1. We also appreciate access to summary data provided by the Psychiatric Genomics Consortium (PGC) Substance Use Disorders (SUD) working group. The PGC-SUD is supported by funds from NIDA and NIMH to MH109532 and, previously, had analyst support from NIAAA to U01AA008401 (COGA). PGC-SUD gratefully acknowledges its contributing studies and the participants in those studies without whom this effort would not be possible.
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
- Physics and Astronomy (all)
- Chemistry (all)
- Biochemistry, Genetics and Molecular Biology (all)