Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures.
- Authors
- Kapoor, M; Chou, Y-L; Edenberg, H J; Foroud, T; Martin, N G; Madden, P A F; Wang, J C; Bertelsen, S; Wetherill, L; Brooks, A; Chan, G; Hesselbrock, V; Kuperman, S; Medland, S E; Montgomery, G; Tischfield, J; Whitfield, J B; Bierut, L J; Heath, A C; Bucholz, K K; Goate, A M; Agrawal, A
- Year
- 2016
- Journal
- Translational psychiatry
- PMID
- 27003187
- DOI
- 10.1038/tp.2016.27
- PMCID
- PMC4872451
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.
GRS generated from an analysis of AO-AD in a discovery sample, at varying P-value thresholds, predicting (a) AO-AD, (b) AO-I, (c ) AD, (d) AD-SX, (e) Maxdrinks and (f) height in SAGE dataset. The x-axis represents the GRS thresholds and y-axis represents the adjusted R2 for the trait. Each bar represents the values of adjusted R2 for SAGE. Colors of the bar represent the level of significance achieved. AD, alcohol dependence; AD-SX, total number of DSM4 AD symptoms endorsed; AO-AD, age at onset of AD; AO-I, age at onset of intoxication; GRS, genome-wide polygenic scores; SAGE, Study of Addictions: Genes and Environment.
GRS generated from an analysis of AO-AD in a discovery sample, at varying P-value thresholds, predicting (a) AO-AD, (b) AO-I, (c ) AD, (d) AD-SX, (e) Maxdrinks and (f) height in OZ-ALC dataset. The x-axis represents the GRS thresholds and y-axis represents the adjusted R2 for the trait. Each bar represents the values of adjusted R2 for OZ-ALC. Colors of the bar represent the significance level achieved. AD, alcohol dependence; AD-SX, total number of DSM4 AD symptoms endorsed; AO-AD, age at onset of AD; AO-I, age at onset of intoxication; GRS, genome-wide polygenic scores.
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