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Transl Psychiatry. 2016 Mar 22;6:e761. doi: 10.1038/tp.2016.27.

Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures.

Author information

1
Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2
Washington University School of Medicine, St. Louis, MO, USA.
3
Indiana University School of Medicine, Indianapolis, IN, USA.
4
Queensland Institute of Medical Research, Brisbane, QLD, Australia.
5
Rutgers University, New Brunswick, NJ, USA.
6
University of Connecticut Health Center, Farmington, CT, USA.
7
University of Iowa Carver College of Medicine, Iowa City, IA, USA.

Abstract

Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.

PMID:
27003187
PMCID:
PMC4872451
DOI:
10.1038/tp.2016.27
[Indexed for MEDLINE]
Free PMC Article

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