title: Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population-based cohort.
abstract: 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.
authors: Division of Psychiatry.
authors: Toni-Kim
authors: TK
authors: Clarke
authors: Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, VA CT Healthcare Center, West Haven, CT, USA.|Medical Scientist Training Program and Interdepartmental Neuroscience Program, Yale University School of Medicine, West Haven, CT, USA.
authors: Andrew H
authors: AH
authors: Smith
authors: Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, VA CT Healthcare Center, West Haven, CT, USA.|Department of Genetics and Neurobiology, Yale University School of Medicine, West Haven, CT, USA.
authors: Joel
authors: J
authors: Gelernter
authors: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, VISN4 MIRECC, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors: Henry R
authors: HR
authors: Kranzler
authors: Departments of Medicine, Neurology, Ophthalmology, Biomedical Genetics, Epidemiology, and Biostatistics, Boston University School of Medicine and Public Health, Boston, MA, USA.
authors: Lindsay A
authors: LA
authors: Farrer
authors: Division of Psychiatry.
authors: Lynsey S
authors: LS
authors: Hall
authors: Division of Psychiatry.
authors: Ana M
authors: AM
authors: Fernandez-Pujals
authors: Division of Psychiatry.
authors: Donald J
authors: DJ
authors: MacIntyre
authors: Population Health Sciences, University of Dundee, UK.
authors: Blair H
authors: BH
authors: Smith
authors: Division of Applied Health Sciences, University of Aberdeen, UK.
authors: Lynne J
authors: LJ
authors: Hocking
authors: Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK.
authors: Sandosh
authors: S
authors: Padmanabhan
authors: Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, UK.|MRC Human Genetics, MRC IGMM, University of Edinburgh, UK.
authors: Caroline
authors: C
authors: Hayward
authors: Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, UK.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK.
authors: Pippa A
authors: PA
authors: Thomson
authors: MRC Human Genetics, MRC IGMM, University of Edinburgh, UK.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK.
authors: David J
authors: DJ
authors: Porteous
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK.|Department of Psychology, University of Edinburgh, UK.
authors: Ian J
authors: IJ
authors: Deary
authors: Division of Psychiatry.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK.
authors: Andrew M
authors: AM
authors: McIntosh
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D004522:Educational Status; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology; D012959:Socioeconomic Factors
keywords: Alcohol dependence; cognition; environment; genetics; polygenic; social deprivation