Polygenic risk for alcohol dependence associates with alcohol consumption, cognitive function and social deprivation in a population-based cohort.
paper
Primary
Public
- Authors
- Clarke, Toni-Kim; Smith, Andrew H; Gelernter, Joel; Kranzler, Henry R; Farrer, Lindsay A; Hall, Lynsey S; Fernandez-Pujals, Ana M; MacIntyre, Donald J; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; Thomson, Pippa A; Porteous, David J; Deary, Ian J; McIntosh, Andrew M
- Year
- 2016
- Journal
- Addiction biology
- PMID
- 25865819
- DOI
- 10.1111/adb.12245
- PMCID
- PMC4600406
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.
Figure 1
(a) Proportion of variance in alcohol consumption and cognitive variables explained by SAGE AD polygenic risk score derived using five different P‐value thresholds. (b) Proportion of variance in alcohol consumption and cognitive variables explained by Yale‐Penn AD polygenic risk score derived using five different P‐value thresholds. DSC = digit symbol coding; g_kg = grams of ethanol per kg of body weight consumed per week; MHV = Mill Hill vocabulary; VF = verbal fluency. Only tests significantly associated with AD polygenic risk score from both Yale‐Penn and SAGE GWAS at the P‐value threshold P ≤ 0.5 are presented.
Figure 2
Relationship of alcohol polygenic risk score to MHV in SIMD quintiles
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| Name | Type |
|---|---|
| ACTIVE local | cohort |
| ADH1A | gene |
| ADH1B | gene |
| ADH1C | gene |
| ADH4 | gene |
| ADH5 | gene |
| ADH6 | gene |
| age | phenotype |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| Alcohol dependence PGRS local | drug |
| Alcohol dependence polygenic risk score local | phenotype |
| Alcohol dependence polygenic risk score (PGRS) local | phenotype |
| alcohol dependence risk alleles local | variant |
| Alcohol dependence risk alleles local | variant |
| Alcohol dependence risk score local | phenotype |
| Alcohol-induced hangovers local | phenotype |
| alcoholism | phenotype |
| alcohol-related diseases | phenotype |
| alcohol-related problems | phenotype |
| Alcohol Use | phenotype |
| Alcohol Use Disorder | phenotype |
| alcohol use disorders | phenotype |
| binge drinking | phenotype |
| childhood IQ | phenotype |
| Childhood mental ability local | phenotype |
| children of alcoholics | cohort |
| Chromosome 4 SNPs local | variant |
| cocaine | phenotype |
| COGEND | cohort |
| cognition | phenotype |
| cognitive ability | phenotype |
| cognitive measures | phenotype |
| Cognitive variables local | phenotype |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| cross council Lifelong Health and Wellbeing Initiative local | cohort |
| current drinkers | phenotype |
| Digit symbol coding local | phenotype |
| Digit Symbol Coding local | phenotype |
| education | phenotype |
| educational attainment | phenotype |
| education (years of schooling) local | phenotype |
| ENIGMA 1000 genomes protocol local | drug |
| executive function | phenotype |
| family history of alcoholism | phenotype |
| former drinker | phenotype |
| frontal cortex | anatomy |
| FSCD | cohort |
| Gene Environment Association Studies | cohort |
| Generation Scotland | cohort |
| Generation Scotland: Scottish Family Health Study local | cohort |
| Geneva | cohort |
| GENEVA Coordinating Center local | cohort |
| HapMap CEU | cohort |
| Harmful drinking behaviour local | phenotype |
| hazardous drinking | phenotype |
| Health Survey (2003/2004–2007) local | cohort |
| healthy controls | cohort |
| High genetic risk individuals local | cohort |
| IlluminaGenomeStudio Analysis software v2011.1 local | drug |
| IlluminaHumanOmniExpressExome-8v1.0 BeadChip local | drug |
| Independent schizophrenia cohort local | cohort |
| Infinum chemistry local | drug |
| intelligence | phenotype |
| language ability | phenotype |
| Large population-based sample local | cohort |
| Low-income households local | phenotype |
| men | cohort |
| Mill Hill Vocabulary local | phenotype |
| Mill Hill Vocabulary test local | phenotype |
| Mill Hill Vocabulary test performance local | phenotype |
| Most socially deprived regions local | phenotype |
| nicotine | drug |
| Non-dependent offspring of alcoholics local | cohort |
| non-drinkers | phenotype |
| opioid | drug |
| opioid dependence | phenotype |
| PGRS local | variant |
| PGRS_GS:SFHS local | drug |
| PGRS_SAGE local | drug |
| PGRS_Yale-Penn local | drug |
| Phonemic verbal fluency local | phenotype |
| Plink | drug |
| polygenic risk for alcohol dependence local | variant |
| Polygenic risk for alcohol dependence local | phenotype |
| Polygenic risk score for alcohol dependence | phenotype |
| Positive family history of alcohol dependence local | phenotype |
| prefrontal cortex | anatomy |
| problematic alcohol use | phenotype |
| processing speed | phenotype |
| SAGE | cohort |
| schizophrenia | phenotype |
| Schizophrenia Working Group of Psychiatric Genetics Consortium 2014 local | cohort |
| Scottish Health Survey 2012 local | cohort |
| Scottish Index of Multiple Deprivation (SIMD) local | phenotype |
| Scottish population-based sample local | cohort |
| sex | phenotype |
| SIMD quintile 1 local | cohort |
| SIMD quintile 5 local | cohort |
| SNP | cohort |
| Social and personal adversity local | phenotype |
| social deprivation | phenotype |
| socio-economic deprivation | phenotype |
| socio-economic status | phenotype |
| Study of Addiction: Genetics and Environment | cohort |
| topiramate | drug |
| University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology local | cohort |
| unrelated individuals | cohort |
| verbal declarative memory local | phenotype |
| verbal fluency | phenotype |
| verbal fluency test local | phenotype |
| Wellcome Trust Clinical Research Facility Genetics Core, Edinburgh local | cohort |
| Welsh Health Survey 2003/2004–2007 local | cohort |
| Yale GWAS study local | cohort |
| Yale-Penn | cohort |
| Yale-Penn/SAGE samples local | cohort |
| Years in education local | phenotype |
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