TY - JOUR
T1 - The role of parental genotype in the intergenerational transmission of externalizing behavior
T2 - Evidence for genetic nurturance
AU - Kuo, Sally I.Chun
AU - Poore, Holly E.
AU - Barr, Peter B.
AU - Chirico, Isabella S.
AU - Aliev, Fazil
AU - Bucholz, Kathleen K.
AU - Chan, Grace
AU - Kamarajan, Chella
AU - Kramer, John R.
AU - McCutcheon, Vivia V.
AU - Plawecki, Martin H.
AU - Dick, Danielle M.
N1 - Funding Information:
This study was funded by the National Institutes of Health through the National Institute on Alcohol Abuse and Alcoholism (U10AA008401) and the National Institute on Drug Abuse (R01DA050721).
Funding Information:
The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, T. Foroud; Scientific Director, A. Agrawal; Translational Director, D. Dick, includes eleven different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, T. Foroud, Y. Liu, M. Plawecki); University of Iowa Carver College of Medicine (S. Kuperman, J. Kramer); SUNY Downstate Health Sciences University (B. Porjesz, J. Meyers, C. Kamarajan, A. Pandey); Washington University in St. Louis (L. Bierut, J. Rice, K. Bucholz, A. Agrawal); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield, R. Hart, J. Salvatore); The Children’s Hospital of Philadelphia, University of Pennsylvania (L. Almasy); Virginia Commonwealth University (D. Dick); Icahn School of Medicine at Mount Sinai (A. Goate, P. Slesinger); and Howard University (D. Scott). Other COGA collaborators include: L. Bauer (University of Connecticut); J. Nurnberger Jr., L. Wetherill, X. Xuei, D. Lai, S. O’Connor, (Indiana University); G. Chan (University of Iowa; University of Connecticut); D.B. Chorlian, J. Zhang, P. Barr, S. Kinreich, G. Pandey (SUNY Downstate); N. Mullins (Icahn School of Medicine at Mount Sinai); A. Anokhin, S. Hartz, E. Johnson, V. McCutcheon, S. Saccone (Washington University); J. Moore, Z. Pang, S. Kuo (Rutgers University); A. Merikangas (The Children’s Hospital of Philadelphia and University of Pennsylvania); F. Aliev (Virginia Commonwealth University); H. Chin and A. Parsian are the National Institute on Alcohol Abuse and Alcoholism Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse.
Funding Information:
The Externalizing Consortium has been supported by the National Institute of Alcohol Abuse and Alcoholism (R01AA015146 – 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). 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 for making its 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.
Publisher Copyright:
©
PY - 2022/12/6
Y1 - 2022/12/6
N2 - The purpose of this study was to examine possible pathways by which genetic risk associated with externalizing is transmitted in families. We used molecular data to disentangle the genetic and environmental pathways contributing to adolescent externalizing behavior in a sample of 1,111 adolescents (50% female; 719 European and 392 African ancestry) and their parents from the Collaborative Study on the Genetics of Alcoholism. We found evidence for genetic nurture such that parental externalizing polygenic scores were associated with adolescent externalizing behavior, over and above the effect of adolescents' own externalizing polygenic scores. Mediation analysis indicated that parental externalizing psychopathology partly explained the effect of parental genotype on children's externalizing behavior. We also found evidence for evocative gene-environment correlation, whereby adolescent externalizing polygenic scores were associated with lower parent-child communication, less parent-child closeness, and lower parental knowledge, controlling for parental genotype. These effects were observed among participants of European ancestry but not African ancestry, likely due to the limited predictive power of polygenic scores across ancestral background. These results demonstrate that in addition to genetic transmission, genes influence offspring behavior through the influence of parental genotypes on their children's environmental experiences, and the role of children's genotypes in shaping parent-child relationships.
AB - The purpose of this study was to examine possible pathways by which genetic risk associated with externalizing is transmitted in families. We used molecular data to disentangle the genetic and environmental pathways contributing to adolescent externalizing behavior in a sample of 1,111 adolescents (50% female; 719 European and 392 African ancestry) and their parents from the Collaborative Study on the Genetics of Alcoholism. We found evidence for genetic nurture such that parental externalizing polygenic scores were associated with adolescent externalizing behavior, over and above the effect of adolescents' own externalizing polygenic scores. Mediation analysis indicated that parental externalizing psychopathology partly explained the effect of parental genotype on children's externalizing behavior. We also found evidence for evocative gene-environment correlation, whereby adolescent externalizing polygenic scores were associated with lower parent-child communication, less parent-child closeness, and lower parental knowledge, controlling for parental genotype. These effects were observed among participants of European ancestry but not African ancestry, likely due to the limited predictive power of polygenic scores across ancestral background. These results demonstrate that in addition to genetic transmission, genes influence offspring behavior through the influence of parental genotypes on their children's environmental experiences, and the role of children's genotypes in shaping parent-child relationships.
KW - Keywords: Adolescent externalizing
KW - gene-environment correlation
KW - genetic nurture
KW - parenting
KW - polygenic score
UR - http://www.scopus.com/inward/record.url?scp=85145240566&partnerID=8YFLogxK
U2 - 10.1017/S0954579422000700
DO - 10.1017/S0954579422000700
M3 - Article
C2 - 36200344
AN - SCOPUS:85145240566
SN - 0954-5794
VL - 34
SP - 1865
EP - 1875
JO - Development and Psychopathology
JF - Development and Psychopathology
IS - 5
ER -