Mapping Pathways by Which Genetic Risk Influences Adolescent Externalizing Behavior: The Interplay Between Externalizing Polygenic Risk Scores, Parental Knowledge, and Peer Substance Use.
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- Authors
- Kuo, Sally I-Chun; Salvatore, Jessica E; Barr, Peter B; Aliev, Fazil; Anokhin, Andrey; Bucholz, Kathleen K; Chan, Grace; Edenberg, Howard J; Hesselbrock, Victor; Kamarajan, Chella; Kramer, John R; Lai, Dongbing; Mallard, Travis T; Nurnberger, John I; Pandey, Gayathri; Plawecki, Martin H; Sanchez-Roige, Sandra; Waldman, Irwin; Palmer, Abraham A; Externalizing Consortium; Dick, Danielle M
- Year
- 2021
- Journal
- Behavior genetics
- PMID
- 34117972
- DOI
- 10.1007/s10519-021-10067-7
- PMCID
- PMC8403154
Genetic predispositions and environmental influences both play an important role in adolescent externalizing behavior; however, they are not always independent. To elucidate gene-environment interplay, we examined the interrelationships between externalizing polygenic risk scores, parental knowledge, and peer substance use in impacting adolescent externalizing behavior across two time-points in a high-risk longitudinal sample of 1,200 adolescents (764 European and 436 African ancestry; M = 12.99) from the Collaborative Study on the Genetics of Alcoholism. Results from multivariate path analysis indicated that externalizing polygenic scores were directly associated with adolescent externalizing behavior but also indirectly via peer substance use, in the European ancestry sample. No significant polygenic association nor indirect effects of genetic risk were observed in the African ancestry group, likely due to more limited power. Our findings underscore the importance of gene-environment interplay and suggest peer substance use may be a mechanism through which genetic risk influences adolescent externalizing behavior.
Conceptual model of the associations among externalizing polygenic score, parental knowledge, peer substance use, and adolescent externalizing behaviors and their interplayNote. a = direct genetic effect on Time 1 (T1) externalizing behavior. b = direct genetic effect on T1 parental knowledge. c = direct genetic effect on T1 peer substance use. Paths b and c indicate evidence of gene-environment correlations. d = direct effect of T1 parental knowledge on T2 externalizing behavior. e = direct effect of T1 peer substance use on T2 externalizing behavior. f = effect of T1 externalizing behavior on T2 parental knowledge. g = effect of T1 externalizing behavior on T2 peer substance use. h = effect of T1 parental knowledge on T2 peer substance use. i = effect of T1 peer substance use on T2 parental knowledge.
Path model linking the associations among externalizing polygenic scores, parental knowledge, peer substance use, and adolescent externalizing behaviors at Time 1 and Time 2 among participants of European ancestryNote. Standardized path coefficients are presented. The EXT PGS included in the analyses was regressed on the ten genetic ancestry principal components. To simplify the figure, covariates (age, sex) are not illustrated. Dashed lines represent nonsignificant paths.*p < .05, **p < .01.
Path model linking the associations among externalizing polygenic scores, parental knowledge, peer substance use, and adolescent externalizing behaviors at Time 1 and Time 2 among participants of African ancestryNote. Standardized path coefficients are presented. The EXT PGS included in the analyses was regressed on the ten genetic ancestry principal components. To simplify the figure, covariates (age, sex) are not illustrated. Dashed lines represent nonsignificant paths.*p < .05, **p < .01.
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External
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