Abstract
We tested whether aspects of the childhood/adolescent home environment mediate genetic risk for alcohol problems within families across generations. Parental relationship discord and parental divorce were the focal environments examined. The sample included participants of European ancestry (N = 4806, 51% female) and African ancestry (N = 1960, 52% female) from the high-risk Collaborative Study on the Genetics of Alcoholism. Alcohol outcomes in the child generation included lifetime criterion counts for DSM-5 Alcohol Use Disorder (AUD), lifetime maximum drinks in 24 h, age at initiation of regular drinking, and age at first alcohol intoxication. Predictors in the parent generation included relationship discord, divorce, alcohol measures parallel to those in the child generation, and polygenic scores for alcohol problems. Parental polygenic scores were partitioned into alleles that were transmitted and non-transmitted to the child. The results from structural equation models were consistent with genetic nurture effects in European ancestry families. Exposure to parental relationship discord and parental divorce mediated, in part, the transmission of genetic risk for alcohol problems from parents to children to predict earlier ages regular drinking (βindirect = −0.018 [−0.026, −0.011]) and intoxication (βindirect = −0.015 [−0.023, −0.008]), greater lifetime maximum drinks (βindirect = 0.006 [0.002, 0.01]) and more lifetime AUD criteria (βindirect = 0.011 [0.006, 0.016]). In contrast, there was no evidence that parental alleles had indirect effects on offspring alcohol outcomes via parental relationship discord or divorce in the smaller number of families of African ancestry. In conclusion, parents transmit genetic risk for alcohol problems to their children not only directly, but also indirectly via genetically influenced aspects of the home environment. Further investigation of genetic nurture in non-European samples is needed.
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Acknowledgements
The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, T. Foroud; Scientific Director, A. Agrawal; Translational Director, DD, includes eleven different centers: University of Connecticut (VH); Indiana University (HJE, TF, YL, MP); University of Iowa Carver College of Medicine (SK, JK); SUNY Downstate Health Sciences University (BP, JM, CK, AP); Washington University in St. Louis (LB, JR, KB, AA); University of California at San Diego (MS); Rutgers University (JT, RH, JS); The Children’s Hospital of Philadelphia, University of Pennsylvania (LA); Virginia Commonwealth University (DD); Icahn School of Medicine at Mount Sinai (AG, PS); and Howard University (DS). Other COGA collaborators include: L Bauer (University of Connecticut); J. Nurnberger Jr., L. Wetherill, X., Xuei, D. Lai, S. O’Connor, (Indiana University); GC (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 NIAAA 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 (NIAAA) and the National Institute on Drug Abuse (NIDA). Additional support for this project came from NIAAA award R01AA028064 to JES. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Data curation: NST, SIK, FA. Formal analysis: NST, FA. Conceptualization NST, JES. Writing – Original Draft: NST, JES. Writing – review & editing: NST, JES, SIK, FA, VVM, JMM, KKB, SJB, GC, HJE, CK, JRK, SK, GP, MHP, MAS, DMD. Conception and Design of the COGA Study (COGA Collaborators).
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Thomas, N.S., Salvatore, J.E., Kuo, S.IC. et al. Genetic nurture effects for alcohol use disorder. Mol Psychiatry 28, 759–766 (2023). https://doi.org/10.1038/s41380-022-01816-z
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DOI: https://doi.org/10.1038/s41380-022-01816-z