Mapping Pathways by Which Genetic Risk Influences Adolescent Externalizing Behavior: The Interplay Between Externalizing Polygenic Risk Scores, Parental Knowledge, and Peer Substance Use

Sally I-Chun Kuo; Jessica E Salvatore; Peter B Barr; Fazil Aliev; Andrey Anokhin; Kathleen K Bucholz; Grace Chan; Howard J Edenberg; Victor Hesselbrock; Chella Kamarajan; John R Kramer; Dongbing Lai; Travis T Mallard; John I Nurnberger Jr; Gayathri Pandey; Martin H Plawecki; Sandra Sanchez-Roige; Irwin Waldman; Abraham A Palmer; Externalizing Consortium; Danielle M Dick

doi:10.1007/s10519-021-10067-7

Mapping Pathways by Which Genetic Risk Influences Adolescent Externalizing Behavior: The Interplay Between Externalizing Polygenic Risk Scores, Parental Knowledge, and Peer Substance Use

Behav Genet. 2021 Sep;51(5):543-558. doi: 10.1007/s10519-021-10067-7. Epub 2021 Jun 12.

Authors

Sally I-Chun Kuo¹, Jessica E Salvatore², Peter B Barr², Fazil Aliev², Andrey Anokhin³, Kathleen K Bucholz³, Grace Chan⁴, Howard J Edenberg^{5

6}, Victor Hesselbrock⁴, Chella Kamarajan⁷, John R Kramer⁸, Dongbing Lai⁶, Travis T Mallard⁹, John I Nurnberger Jr⁶, Gayathri Pandey⁷, Martin H Plawecki¹⁰, Sandra Sanchez-Roige^{11

12}, Irwin Waldman¹³, Abraham A Palmer^{11

14}; Externalizing Consortium; Danielle M Dick^{2

15}

Affiliations

¹ Department of Psychology, Virginia Commonwealth University, Box 842018, 806 W Franklin St, Richmond, VA, 23284, USA. ickuo@vcu.edu.
² Department of Psychology, Virginia Commonwealth University, Box 842018, 806 W Franklin St, Richmond, VA, 23284, USA.
³ Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
⁴ Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA.
⁵ Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA.
⁶ Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.
⁷ Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
⁸ Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
⁹ Department of Psychology, University of Texas at Austin, Austin, TX, USA.
¹⁰ Department of Psychiatry, Indiana University, Indianapolis, IN, USA.
¹¹ Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
¹² Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹³ Department of Psychology, Emory University, Atlanta, GA, USA.
¹⁴ Institute of Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
¹⁵ Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.

Abstract

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.

Keywords: Adolescent externalizing; Gene–environment interplay; Parenting; Peers; Polygenic score.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adolescent
Adolescent Behavior*
Child
Humans
Longitudinal Studies
Multifactorial Inheritance / genetics
Parenting
Parents
Peer Group
Risk Factors
Substance-Related Disorders* / genetics

Abstract

Publication types

MeSH terms

Grants and funding