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Updated: May 31, 2026

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
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Gene-Environment Interplay Beyond Interactions: Psychosocial Environments Mediate Genetic Effects Underlying

LiChen Dong1,2,3, A Brooke Sasia1,2,3, James J Li1,2,3

  • 1Department of Psychology, University of Wisconsin-Madison.

Clinical Psychological Science : a Journal of the Association for Psychological Science
|May 29, 2026
PubMed
Summary
This summary is machine-generated.

Genetic predispositions for externalizing behaviors influence substance use and antisocial trajectories indirectly through psychosocial environments, particularly peer affiliations. These findings highlight the significant role of peer influence in gene-environment interplay for behavioral development.

Keywords:
developmentexternalizing behaviorgene-environment interplayindirect effectspolygenic scores

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Area of Science:

  • Behavioral genetics
  • Developmental psychology
  • Psychosocial development

Background:

  • Externalizing (EXT) behaviors encompass substance use (SUB) and antisocial behaviors (ASB).
  • Gene-environment interplay is crucial for understanding the developmental trajectories of EXT behaviors.
  • Previous research has identified polygenic scores (PGS) associated with EXT behaviors.

Purpose of the Study:

  • To investigate how adolescent psychosocial environments moderate and mediate the effects of EXT polygenic scores (PGS) on substance use (SUB) and antisocial behavior (ASB) trajectories.
  • To examine gene-environment interplay in diverse genetic similarity groups.
  • To elucidate the indirect pathways through which genetic predispositions influence long-term behavioral development.

Main Methods:

  • Utilized data from the Add Health study, analyzing latent trajectories of SUB and ASB from ages 13 to 41.
  • Modeled adolescent psychosocial environments (parenting, peer affiliation, school/neighborhood connectedness) as moderators and mediators.
  • Examined effects of EXT PGS in European, African, Asian, and Hispanic genetic similarity groups.

Main Results:

  • No evidence of moderation effects of psychosocial environments on the direct influence of EXT PGS.
  • Significant indirect effects of EXT PGS on SUB and ASB trajectories were observed, mediated by psychosocial environments.
  • Delinquent peer affiliation emerged as a key mediator, highlighting its role in the gene-environment interplay for EXT behaviors.

Conclusions:

  • Genetic predispositions for externalizing behaviors do not operate in isolation but are significantly shaped by psychosocial factors.
  • Peer influences, specifically delinquent peer affiliation, play a critical role in mediating the impact of genetic risk on externalizing behavior trajectories.
  • Understanding these indirect pathways is essential for developing effective interventions for externalizing behaviors.