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

• Persistent URL: No alternate ID available
• Type of Material: Article
• Authors: Toni-Kim Clarke, Yale University; Andrew H. Smith, Yale University; Joel Gelernter, Yale University; Henry R. Kranzler, University of Pennsylvania; Lindsay A. Farrer, Boston University; Lynsey S. Hall, Yale University; Ana M. Fernandez-Pujals, Yale University; Donald J. MacIntyre, Yale University; Blair H. Smith, University of Dundee; Lynne J. Hocking, University of Aberdeen; Sandosh Padmanabhan, University of Glasgow; Caroline Hayward, University of Edinburgh; Pippa A. Thomson, University of Edinburgh; David J. Porteous, University of Edinburgh; Ian J. Deary, University of Edinburgh; Andrew M. McIntosh, Yale University; Alicia K Smith, Emory University
• Language: English
• Date: 2016-03-01
• Publisher: Wiley: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 2015 The Authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/adb.12245
• Title of Journal or Parent Work: Addiction Biology
• ISSN: 1355-6215
• Volume: 21
• Issue: 2
• Start Page: 469
• End Page: 480
• Grant/Funding Information: CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (Contract No. N01‐HG‐65403).; GS:SFHS was funded by a grant from the Scottish Government Health Department, Chief Scientist Office (No. CZD/16/6).; This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/14/Z.; Assistance with data cleaning was provided by the National Center for Biotechnology Information.; Genotyping services for a part of the Yale GWAS study were provided by the Center for Inherited Disease Research (CIDR) and Yale University (Center for Genome Analysis).; The Chief Scientist Office of the Scottish Government and the Scottish Funding Council provided core support for Generation Scotland.; Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract ‘High throughput genotyping for studying the genetic contributions to human disease’ (HHSN268200782096C).; Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446).; Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged, supported in part by National Institutes of Health grants RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, P50 AA12870, MSTP T32GM07205 and CTSA 8UL1TR000142.; Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [GEI] (U01 HG004422).; SAGE is one of the genome‐wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI.; Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392) and the Family Study of Cocaine Dependence (FSCD; R01 DA013423).; The authors TKC and AMM acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation.
• Keywords: Educational Status; Risk Factors; Polymorphism, Single Nucleotide; Alcohol dependence; Prevalence; Genotype; environment; social deprivation; cognition; Scotland; Gene Frequency; Humans; Multifactorial Inheritance; Cohort Studies; Cognition Disorders; Alcohol Drinking; Middle Aged; Female; genetics; Male; Alcoholism; polygenic; Socioeconomic Factors; Cognition
• Research Categories: Biology, Genetics; Psychology, Social; Health Sciences, Public Health

Abstract

Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction. 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.