TY - JOUR
T1 - Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations
AU - Kranzler, Henry R.
AU - Zhou, Hang
AU - Kember, Rachel L.
AU - Vickers Smith, Rachel
AU - Justice, Amy C.
AU - Damrauer, Scott
AU - Tsao, Philip S.
AU - Klarin, Derek
AU - Baras, Aris
AU - Reid, Jeffrey
AU - Overton, John
AU - Rader, Daniel J.
AU - Cheng, Zhongshan
AU - Tate, Janet P.
AU - Becker, William C.
AU - Concato, John
AU - Xu, Ke
AU - Polimanti, Renato
AU - Zhao, Hongyu
AU - Gelernter, Joel
N1 - 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.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-09480-8
DO - 10.1038/s41467-019-09480-8
M3 - Article
C2 - 30940813
AN - SCOPUS:85063757709
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1499
ER -