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Genes 2014, 5(2), 330-346;

Polygenic Scores Predict Alcohol Problems in an Independent Sample and Show Moderation by the Environment

Department of Psychiatry, Virginia Commonwealth University, P.O. Box 980126, Richmond, VA 23298, USA
School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK
Translational Research Institute, University of Queensland, Level 7, 37 Kent Street, Woolloongabba, Brisbane QLD 4102, Queensland, Australia
Diamantina Institute, University of Queensland, Level 7, 37 Kent Street, Woolloongabba, Brisbane QLD 4102, Queensland, Australia
Division of Psychiatry, University College London, 67-73 Riding House St., London W1W 7EJ, UK
Department of Public Health, Hjelt Institute, University of Helsinki, P.O. Box 41, Helsinki FI-00014, Finland
National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, P.O. Box 30, Mannerheimintie 166, Helsinki FI-00300, Finland
Department of Psychological and Brain Sciences, Indiana University, 1101 East 10th St., Bloomington, IN 47405, USA
University of Helsinki, Institute for Molecular Medicine (FIMM), P.O. Box 20, Tukholmankatu 8, Helsinki FI-00014, Finland
Authors to whom correspondence should be addressed.
Received: 31 December 2013 / Revised: 20 March 2014 / Accepted: 27 March 2014 / Published: 10 April 2014
(This article belongs to the Special Issue Grand Celebration: 10th Anniversary of the Human Genome Project)
PDF [166 KB, uploaded 10 April 2014]


Alcohol problems represent a classic example of a complex behavioral outcome that is likely influenced by many genes of small effect. A polygenic approach, which examines aggregate measured genetic effects, can have predictive power in cases where individual genes or genetic variants do not. In the current study, we first tested whether polygenic risk for alcohol problems—derived from genome-wide association estimates of an alcohol problems factor score from the age 18 assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4304 individuals of European descent; 57% female)—predicted alcohol problems earlier in development (age 14) in an independent sample (FinnTwin12; n = 1162; 53% female). We then tested whether environmental factors (parental knowledge and peer deviance) moderated polygenic risk to predict alcohol problems in the FinnTwin12 sample. We found evidence for both polygenic association and for additive polygene-environment interaction. Higher polygenic scores predicted a greater number of alcohol problems (range of Pearson partial correlations 0.07–0.08, all p-values ≤ 0.01). Moreover, genetic influences were significantly more pronounced under conditions of low parental knowledge or high peer deviance (unstandardized regression coefficients (b), p-values (p), and percent of variance (R2) accounted for by interaction terms: b = 1.54, p = 0.02, R2 = 0.33%; b = 0.94, p = 0.04, R2 = 0.30%, respectively). Supplementary set-based analyses indicated that the individual top single nucleotide polymorphisms (SNPs) contributing to the polygenic scores were not individually enriched for gene-environment interaction. Although the magnitude of the observed effects are small, this study illustrates the usefulness of polygenic approaches for understanding the pathways by which measured genetic predispositions come together with environmental factors to predict complex behavioral outcomes. View Full-Text
Keywords: alcohol problems; adolescence; gene-by-environment; ALSPAC; FinnTwin12 alcohol problems; adolescence; gene-by-environment; ALSPAC; FinnTwin12
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Salvatore, J.E.; Aliev, F.; Edwards, A.C.; Evans, D.M.; Macleod, J.; Hickman, M.; Lewis, G.; Kendler, K.S.; Loukola, A.; Korhonen, T.; Latvala, A.; Rose, R.J.; Kaprio, J.; Dick, D.M. Polygenic Scores Predict Alcohol Problems in an Independent Sample and Show Moderation by the Environment. Genes 2014, 5, 330-346.

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