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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.

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


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.

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