title: Polygenic scores predict alcohol problems in an independent sample and show moderation by the environment.
abstract: 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.
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, P.O. Box 980126, Richmond, VA 23298, USA. jesalvatore@vcu.edu.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Salvatore
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, P.O. Box 980126, Richmond, VA 23298, USA. faliev@vcu.edu.
authors.forename: Fazil
authors.initials: F
authors.lastname: Aliev
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, P.O. Box 980126, Richmond, VA 23298, USA. edwards.alexis@gmail.com.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Edwards
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK. Dave.Evans@bristol.ac.uk.
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK. john.macleod@bristol.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Macleod
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK. matthew.hickman@bristol.ac.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hickman
authors.affiliation: Division of Psychiatry, University College London, 67-73 Riding House St., London W1W 7EJ, UK. glyn.lewis@ucl.ac.uk.
authors.forename: Glyn
authors.initials: G
authors.lastname: Lewis
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, P.O. Box 980126, Richmond, VA 23298, USA. kendler@vcu.edu.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.affiliation: Department of Public Health, Hjelt Institute, University of Helsinki, P.O. Box 41, Helsinki FI-00014, Finland. antti.latvala@helsinki.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Loukola
authors.affiliation: Department of Public Health, Hjelt Institute, University of Helsinki, P.O. Box 41, Helsinki FI-00014, Finland. tellervo.korhonen@helsinki.fi.
authors.forename: Tellervo
authors.initials: T
authors.lastname: Korhonen
authors.affiliation: Department of Public Health, Hjelt Institute, University of Helsinki, P.O. Box 41, Helsinki FI-00014, Finland. antti.latvala@helsinki.fi.
authors.forename: Antti
authors.initials: A
authors.lastname: Latvala
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, 1101 East 10th St., Bloomington, IN 47405, USA. rose@indiana.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rose
authors.affiliation: Department of Public Health, Hjelt Institute, University of Helsinki, P.O. Box 41, Helsinki FI-00014, Finland. jaakko.kaprio@helsinki.fi.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, P.O. Box 980126, Richmond, VA 23298, USA. ddick@vcu.edu.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
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