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_age = 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.

遗传倾向和环境影响在青少年外化行为中都发挥着重要作用；然而，它们并不总是独立的。为了阐明基因与环境的相互作用，我们在 1,200 名青少年（764 名欧洲青少年和 436 名非洲青少年）的高风险纵向样本中，在两个时间点上检查了外化多基因风险评分、父母知识和同伴物质使用对青少年外化行为的影响之间的相互关系。血统； M_年龄= 12.99）来自酒精中毒遗传学合作研究。多变量路径分析的结果表明，在欧洲血统样本中，外化多基因评分与青少年外化行为直接相关，但也通过同伴物质使用间接相关。在非洲血统组中没有观察到显着的多基因关联或遗传风险的间接影响，这可能是由于功效更有限。我们的研究结果强调了基因与环境相互作用的重要性，并表明同伴物质使用可能是遗传风险影响青少年外化行为的一种机制。