Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population-based cohort

Clarke, T.-K. et al. (2016) Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population-based cohort. Addiction Biology, 21(2), pp. 469-480. (doi: 10.1111/adb.12245) (PMID:25865819) (PMCID:PMC4600406)

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Alcohol dependence is frequently co-morbid with cognitive impairment. The relationship between these traits is complex as cognitive dysfunction may arise as a consequence of heavy drinking or exist prior to the onset of dependence. In the present study, we tested the genetic overlap between cognitive abilities and alcohol dependence using polygenic risk scores (PGRS). We created two independent PGRS derived from two recent genome-wide association studies (GWAS) of alcohol dependence (SAGE GWAS: n = 2750; Yale-Penn GWAS: n = 2377) in a population-based cohort, Generation Scotland: Scottish Family Health Study (GS:SFHS) (n = 9863). Data on alcohol consumption and four tests of cognitive function [Mill Hill Vocabulary (MHV), digit symbol coding, phonemic verbal fluency (VF) and logical memory] were available. PGRS for alcohol dependence were negatively associated with two measures of cognitive function: MHV (SAGE: P = 0.009, β = −0.027; Yale-Penn: P = 0.001, β = −0.034) and VF (SAGE: P = 0.0008, β = −0.036; Yale-Penn: P = 0.00005, β = −0.044). VF remained robustly associated after adjustment for education and social deprivation; however, the association with MHV was substantially attenuated. Shared genetic variants may account for some of the phenotypic association between cognitive ability and alcohol dependence. A significant negative association between PGRS and social deprivation was found (SAGE: P = 5.2 × 10−7, β = −0.054; Yale-Penn: P = 0.000012, β = −0.047). Individuals living in socially deprived regions were found to carry more alcohol dependence risk alleles which may contribute to the increased prevalence of problem drinking in regions of deprivation. Future work to identify genes which affect both cognitive impairment and alcohol dependence will help elucidate biological processes common to both disorders.

Item Type:Articles
Additional Information:Funded by: Scottish Government Health Department, Chief Scientist Office. Grant Number: CZD/16/6 National Institutes of Health. Grant Numbers: N01-HG-65403, HHSN268200782096C, RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, P50 AA12870, MSTP T32GM07205, CTSA 8UL1TR000142 NIH Genes, Environment and Health Initiative [GEI]. Grant Numbers: U01 HG004422, U01HG004438 Gene Environment Association Studies (GENEVA). Grant Number: U01 HG004446 Collaborative Study on the Genetics of Alcoholism. Grant Number: U10 AA008401 Collaborative Genetic Study of Nicotine Dependence. Grant Number: P01 CA089392 Family Study of Cocaine Dependence. Grant Number: R01 DA013423 National Institute on Alcohol Abuse and Alcoholism National Institute on Drug Abuse Dr Mortimer and Theresa Sackler Foundation Biotechnology and Biological Sciences Research Council (BBSRC) Medical Research Council (MRC)
Glasgow Author(s) Enlighten ID:Padmanabhan, Professor Sandosh
Authors: Clarke, T.-K., Smith, A. H., Gelernter, J., Kranzler, H. R., Farrer, L. A., Hall, L. S., Fernandez-Pujals, A. M., MacIntyre, D. J., Smith, B. H., Hocking, L. J., Padmanabhan, S., Hayward, C., Thomson, P. A., Porteous, D. J., Deary, I. J., and McIntosh, A. M.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Addiction Biology
Publisher:Wiley-Blackwell Publishing Ltd.
ISSN (Online):1369-1600
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Addiction Biology 21(2): 469-480
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
381721Generation ScotlandAnna DominiczakScottish Executive Health Department (SEHHD-CSO)CZD/16/6RI CARDIOVASCULAR & MEDICAL SCIENCES