title: Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures.
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.
authors.affiliation: Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Chou
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: N G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: P A F
authors.initials: PA
authors.lastname: Madden
authors.affiliation: Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bertelsen
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wetherill
authors.affiliation: Rutgers University, New Brunswick, NJ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Brooks
authors.affiliation: University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: G
authors.initials: G
authors.lastname: Chan
authors.affiliation: University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: V
authors.initials: V
authors.lastname: Hesselbrock
authors.affiliation: University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kuperman
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: S E
authors.initials: SE
authors.lastname: Medland
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Montgomery
authors.affiliation: Rutgers University, New Brunswick, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tischfield
authors.affiliation: Queensland Institute of Medical Research, Brisbane, QLD, Australia.
authors.forename: J B
authors.initials: JB
authors.lastname: Whitfield
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Bierut
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Heath
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Bucholz
authors.affiliation: Neuroscience Genetics & Genomics Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Goate
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: A
authors.initials: A
authors.lastname: Agrawal
mesh_terms: D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000235:genetics*; D001315:Australia; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D010375:Pedigree; D010641:Phenotype; D014481:United States; D044465:White People