Polygenic scores predict alcohol problems in an independent sample and show moderation by the environment

Salvatore, Jessica E., Aliev, Fazil, Edwards, Alexia C., Evans, David M., Macleod, John, Hickman, Matthew, Lewis, Glyn, Kendler, Kenneth S., Loukola, Anu, Korhonen, Tellervo, Latvala, Antti, Rose, Richard J., Kaprio, Jaakko and Dick, Danielle M. (2014) Polygenic scores predict alcohol problems in an independent sample and show moderation by the environment. Genes, 5 2: 330-346. doi:10.3390/genes5020330


Author Salvatore, Jessica E.
Aliev, Fazil
Edwards, Alexia C.
Evans, David M.
Macleod, John
Hickman, Matthew
Lewis, Glyn
Kendler, Kenneth S.
Loukola, Anu
Korhonen, Tellervo
Latvala, Antti
Rose, Richard J.
Kaprio, Jaakko
Dick, Danielle M.
Title Polygenic scores predict alcohol problems in an independent sample and show moderation by the environment
Journal name Genes   Check publisher's open access policy
ISSN 2073-4425
Publication date 2014
Year available 2014
Sub-type Article (original research)
DOI 10.3390/genes5020330
Open Access Status DOI
Volume 5
Issue 2
Start page 330
End page 346
Total pages 17
Place of publication Basel, Switzerland
Publisher MDPI AG
Collection year 2015
Language eng
Subject 1311 Genetics
2716 Genetics (clinical)
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, R = 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.
Keyword Adolescence
Alcohol problems
ALSPAC
FinnTwin12
Gene-by-environment
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
 
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