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

M Kapoor; Y-L Chou; H J Edenberg; T Foroud; N G Martin; P A F Madden; J C Wang; S Bertelsen; L Wetherill; G Chan; V Hesselbrock; S Kuperman; S E Medland; G Montgomery; J Tischfield; J B Whitfield; L J Bierut; A C Heath; K K Bucholz; A M Goate; A Agrawal; Andrew I Brooks

doi:10.1038/tp.2016.27

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

Journal article

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

M Kapoor, Y-L Chou, H J Edenberg, T Foroud, N G Martin, P A F Madden, J C Wang, S Bertelsen, L Wetherill, G Chan, …

Translational psychiatry, Vol.6(3), pp.e761-e761

03/22/2016

DOI: 10.1038/tp.2016.27

PMCID: PMC4872451

PMID: 27003187

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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.

Australia

Phenotype

United States

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

Middle Aged

European Continental Ancestry Group

Male

Multifactorial Inheritance

Pedigree

Age of Onset

Adult

Alcoholism - genetics

Female

Details

Title: Subtitle: Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures
Creators: M Kapoor - Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Y-L Chou - Washington University School of Medicine, St. Louis, MO, USA
H J Edenberg - Indiana University School of Medicine, Indianapolis, IN, USA
T Foroud - Indiana University School of Medicine, Indianapolis, IN, USA
N G Martin - Queensland Institute of Medical Research, Brisbane, QLD, Australia
P A F Madden - Washington University School of Medicine, St. Louis, MO, USA
J C Wang - Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
S Bertelsen - Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
L Wetherill - Indiana University School of Medicine, Indianapolis, IN, USA
G Chan - University of Connecticut Health Center, Farmington, CT, USA
V Hesselbrock - University of Connecticut Health Center, Farmington, CT, USA
S Kuperman - University of Iowa Carver College of Medicine, Iowa City, IA, USA
S E Medland - Queensland Institute of Medical Research, Brisbane, QLD, Australia
G Montgomery - Queensland Institute of Medical Research, Brisbane, QLD, Australia
J Tischfield - Rutgers University, New Brunswick, NJ, USA
J B Whitfield - Queensland Institute of Medical Research, Brisbane, QLD, Australia
L J Bierut - Washington University School of Medicine, St. Louis, MO, USA
A C Heath - Washington University School of Medicine, St. Louis, MO, USA
K K Bucholz - Washington University School of Medicine, St. Louis, MO, USA
A M Goate - Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
A Agrawal - Washington University School of Medicine, St. Louis, MO, USA
Andrew I Brooks
Resource Type: Journal article
Publication Details: Translational psychiatry, Vol.6(3), pp.e761-e761
DOI: 10.1038/tp.2016.27
PMID: 27003187
PMCID: PMC4872451
NLM abbreviation: Transl Psychiatry
ISSN: 2158-3188
eISSN: 2158-3188
Publisher: United States
Grant note: P01CA089392 / NCI NIH HHS UL1 TR001108 / NCATS NIH HHS R01DA019963 / NIDA NIH HHS U01HG004422 / NHGRI NIH HHS K02DA32573 / NIDA NIH HHS R21AA021235 / NIAAA NIH HHS U10AA008401 / NIAAA NIH HHS K05 AA017688 / NIAAA NIH HHS UL1 TR002529 / NCATS NIH HHS R01DA013423 / NIDA NIH HHS
Language: English
Date published: 03/22/2016
Academic Unit: Psychiatry; Stead Family Department of Pediatrics
Record Identifier: 9984003445302771

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