Polygenic scores predict alcohol problems in an independent sample and show moderation by the environment.
- Authors
- Salvatore, Jessica E; Aliev, Fazil; Edwards, Alexis 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
- Year
- 2014
- Journal
- Genes
- PMID
- 24727307
- DOI
- 10.3390/genes5020330
- PMCID
- PMC4094936
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 β€ 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.
Pearson partial correlations (controlling for sex) between polygenic scores and age 14 alcohol problems (all p-values β€ 0.01) in FinnTwin12 (n = 1161).
Parental knowledge (top) and peer deviance (bottom) moderate polygenic risk to predict age 14 alcohol problems in FinnTwin12. Interactions are plotted as predicted values based on the moderated multiple regression equation for age 14 alcohol problems. Illustrative low and high values (Β±1 SD of mean) for the polygenic scores, parental knowledge, and peer deviance are shown. The predicted values for high parental knowledge and low peer deviance were out of bounds (negative values) and were set to zeroβthe lowest possible value for the alcohol problems measure. Error bars are equal to the standard deviation of the model residuals divided by the square root of the sample size. We note that high scores on the parental knowledge scale indicate low parental knowledge (i.e., more risk). For ease of interpretation, we have formatted the axis for each figure so that the riskier environment appears on the right.
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