TY - JOUR
T1 - Gene–environment interplay in externalizing behavior from childhood through adulthood
AU - Kretschmer, Tina
AU - Vrijen, Charlotte
AU - Nolte, Ilja Maria
AU - Wertz, Jasmin
AU - Hartman, Catharina Annette
N1 - This research is part of the TRAILS. Participating centers of TRAILS include various departments of the University Medical Center and the University of Groningen, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Group, all in the Netherlands. TRAILS has been supported by the Netherlands Organization for Scientific Research, ZonMW, GB-MaGW, the Dutch Ministry of Justice, European Science Foundation, European Research Council, BBMRI-NL, and participating universities. The authors are grateful to everyone who participated in this research or worked on this project to make it possible. The authors would like to thank the University of Groningen Center for Information Technology for access to the Peregrine high-performance computing cluster. The polygenic score used here is based on work by the Externalizing Consortium (PIs: Danielle M. Dick, Philipp Koellinger, K. Paige Harden, Abraham A. Palmer. Lead Analysts: Richard Karlsson Linnér, Travis T. Mallard, Peter B. Barr, Sandra Sanchez-Roige. Significant Contributor: Irwin Waldman) which has been supported by the National Institute on Alcohol Abuse and Alcoholism (R01AA015416 – administrative supplement), and the National Institute on Drug Abuse (R01DA050721). Additional funding for investigator effort has been provided by K02AA018755, U10AA008401, P50AA022537, as well as a European Research Council Consolidator Grant (647648 EdGe to Koellinger). The content is solely the responsibility of the authors and does not necessarily represent the official views of the above funding bodies. The Externalizing Consortium would like to thank the following groups for making the research possible: 23andMe, Add Health, Vanderbilt University Medical Center's BioVU, Collaborative Study on the Genetics of Alcoholism (COGA), the Psychiatric Genomics Consortium's Substance Use Disorders working group, UK10K Consortium, UK Biobank, and Philadelphia Neurodevelopmental Cohort. Tina Kretschmer and Charlotte Vrijen are supported by a European Research Council Starting Grant (Grant Agreement Number 757364). Jasmin Wertz was supported by a Postdoctoral Fellowship from the AXA Research Fund at time of writing. The authors have declared that they have no competing or potential conflicts of interest.
Key points
PY - 2022/10
Y1 - 2022/10
N2 - Background: Genetic and environmental influences on externalizing problems are often studied separately. Here, we extended prior work by investigating the implications of gene–environment interplay in childhood for early adult externalizing behavior. Genetic nurture would be indicated if parents' genetic predisposition for externalizing behavior operates through the family environment in predicting offspring early adult externalizing behavior. Evocative gene–environment correlation would be indicated if offspring genetic predisposition for externalizing behavior operates through child externalizing behavior in affecting the family environment and later early adult externalizing behavior. Method: Longitudinal data from seven waves of the TRacking Adolescents' Individual Lives Survey, a prospective cohort study of Dutch adolescents followed from age 11 to age 29 (n at baseline = 2,734) were used. Child externalizing behavior was assessed using self and parent reports. Family dysfunction was assessed by parents. Early adult externalizing behavior was assessed using self-reports. Genome-wide polygenic scores for externalizing problems were constructed for mothers, fathers, and offspring. Results: Offspring polygenic score and child behavior each predicted early adult externalizing problems, as did family dysfunction to a small extent. Parents' polygenic scores were not associated with offspring's early adult externalizing behavior. Indirect effect tests indicated that offspring polygenic score was associated with greater family dysfunction via child externalizing behavior (evocative gene–environment correlation) but the effect was just significant and the effect size was very small. Parents' polygenic scores did not predict family dysfunction, thus the data do not provide support for genetic nurture. Conclusions: A very small evocative gene–environment correlation was detected but effect sizes were much more pronounced for stability in externalizing behavior from childhood through early adulthood, which highlights the necessity to intervene early to prevent later problems.
AB - Background: Genetic and environmental influences on externalizing problems are often studied separately. Here, we extended prior work by investigating the implications of gene–environment interplay in childhood for early adult externalizing behavior. Genetic nurture would be indicated if parents' genetic predisposition for externalizing behavior operates through the family environment in predicting offspring early adult externalizing behavior. Evocative gene–environment correlation would be indicated if offspring genetic predisposition for externalizing behavior operates through child externalizing behavior in affecting the family environment and later early adult externalizing behavior. Method: Longitudinal data from seven waves of the TRacking Adolescents' Individual Lives Survey, a prospective cohort study of Dutch adolescents followed from age 11 to age 29 (n at baseline = 2,734) were used. Child externalizing behavior was assessed using self and parent reports. Family dysfunction was assessed by parents. Early adult externalizing behavior was assessed using self-reports. Genome-wide polygenic scores for externalizing problems were constructed for mothers, fathers, and offspring. Results: Offspring polygenic score and child behavior each predicted early adult externalizing problems, as did family dysfunction to a small extent. Parents' polygenic scores were not associated with offspring's early adult externalizing behavior. Indirect effect tests indicated that offspring polygenic score was associated with greater family dysfunction via child externalizing behavior (evocative gene–environment correlation) but the effect was just significant and the effect size was very small. Parents' polygenic scores did not predict family dysfunction, thus the data do not provide support for genetic nurture. Conclusions: A very small evocative gene–environment correlation was detected but effect sizes were much more pronounced for stability in externalizing behavior from childhood through early adulthood, which highlights the necessity to intervene early to prevent later problems.
KW - externalising disorder
KW - family functioning
KW - gene-environment interaction (GxE)
KW - longitudinal studies
KW - molecular genetics
U2 - 10.1111/jcpp.13652
DO - 10.1111/jcpp.13652
M3 - Article
AN - SCOPUS:85132979254
SN - 0021-9630
VL - 63
SP - 1206
EP - 1213
JO - Journal of Child Psychology and Psychiatry
JF - Journal of Child Psychology and Psychiatry
IS - 10
ER -