PMID- 36253439 OWN - NLM STAT- MEDLINE DCOM- 20230210 LR - 20240327 IS - 1476-5578 (Electronic) IS - 1359-4184 (Print) IS - 1359-4184 (Linking) VI - 28 IP - 2 DP - 2023 Feb TI - Genetic nurture effects for alcohol use disorder. PG - 759-766 LID - 10.1038/s41380-022-01816-z [doi] AB - 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 (beta(indirect) = -0.018 [-0.026, -0.011]) and intoxication (beta(indirect) = -0.015 [-0.023, -0.008]), greater lifetime maximum drinks (beta(indirect) = 0.006 [0.002, 0.01]) and more lifetime AUD criteria (beta(indirect) = 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. CI - (c) 2022. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Thomas, Nathaniel S AU - Thomas NS AUID- ORCID: 0000-0001-6291-0518 AD - Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA. thomasns@vcu.edu. FAU - Salvatore, Jessica E AU - Salvatore JE AUID- ORCID: 0000-0001-5504-5087 AD - Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA. jessica.salvatore@rutgers.edu. FAU - Kuo, Sally I-Chun AU - Kuo SI AUID- ORCID: 0000-0002-6192-1001 AD - Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA. FAU - Aliev, Fazil AU - Aliev F AD - Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA. FAU - McCutcheon, Vivia V AU - McCutcheon VV AD - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. FAU - Meyers, Jacquelyn M AU - Meyers JM AUID- ORCID: 0000-0003-3863-8555 AD - Department of Psychiatry and Behavioral Sciences, State University of New York Health Sciences University, Brooklyn, NY, USA. FAU - Bucholz, Kathleen K AU - Bucholz KK AD - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. FAU - Brislin, Sarah J AU - Brislin SJ AD - Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA. FAU - Chan, Grace AU - Chan G AUID- ORCID: 0000-0002-1257-6889 AD - Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA. AD - Department of Psychiatry, University of Iowa, Iowa City, IA, USA. FAU - Edenberg, Howard J AU - Edenberg HJ AUID- ORCID: 0000-0003-0344-9690 AD - Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA. FAU - Kamarajan, Chella AU - Kamarajan C AUID- ORCID: 0000-0003-2291-6880 AD - Department of Psychiatry and Behavioral Sciences, State University of New York Health Sciences University, Brooklyn, NY, USA. FAU - Kramer, John R AU - Kramer JR AD - Department of Psychiatry, University of Iowa, Iowa City, IA, USA. FAU - Kuperman, Samuel AU - Kuperman S AD - Department of Psychiatry, University of Iowa, Iowa City, IA, USA. FAU - Pandey, Gayathri AU - Pandey G AD - Department of Psychiatry and Behavioral Sciences, State University of New York Health Sciences University, Brooklyn, NY, USA. FAU - Plawecki, Martin H AU - Plawecki MH AUID- ORCID: 0000-0003-0708-9514 AD - Department of Psychiatry, Indiana University, Indianapolis, IN, USA. FAU - Schuckit, Marc A AU - Schuckit MA AD - Department of Psychiatry, University of California San Diego Medical School, San Diego, CA, USA. FAU - Dick, Danielle M AU - Dick DM AUID- ORCID: 0000-0002-1636-893X AD - Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA. CN - COGA Collaborators LA - eng GR - R01 AA028064/AA/NIAAA NIH HHS/United States GR - U24 AG021886/AG/NIA NIH HHS/United States GR - U10 AA008401/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20221017 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 SB - IM MH - Child MH - Adolescent MH - Humans MH - Female MH - Male MH - *Alcoholism/genetics MH - Alcohol Drinking MH - *Alcohol-Related Disorders MH - *Alcoholic Intoxication MH - Risk Factors PMC - PMC10079179 MID - NIHMS1883108 COIS- Conflict of Interest None FIR - Porjesz, Bernice IR - Porjesz B FIR - Hesselbrock, Victor IR - Hesselbrock V FIR - Foroud, Tatiana IR - Foroud T FIR - Agrawal, Arpana IR - Agrawal A FIR - Liu, Yunlong IR - Liu Y FIR - Pandey, Ashwini IR - Pandey A FIR - Bierut, Laura IR - Bierut L FIR - Rice, John IR - Rice J FIR - Tischfield, Jay IR - Tischfield J FIR - Hart, Ronald IR - Hart R FIR - Almasy, Laura IR - Almasy L FIR - Goate, Alison IR - Goate A FIR - Slesinger, Paul IR - Slesinger P FIR - Scott, Denise IR - Scott D EDAT- 2022/10/18 06:00 MHDA- 2023/02/11 06:00 PMCR- 2023/04/06 CRDT- 2022/10/17 23:22 PHST- 2022/04/13 00:00 [received] PHST- 2022/09/23 00:00 [accepted] PHST- 2022/09/19 00:00 [revised] PHST- 2022/10/18 06:00 [pubmed] PHST- 2023/02/11 06:00 [medline] PHST- 2022/10/17 23:22 [entrez] PHST- 2023/04/06 00:00 [pmc-release] AID - 10.1038/s41380-022-01816-z [pii] AID - 10.1038/s41380-022-01816-z [doi] PST - ppublish SO - Mol Psychiatry. 2023 Feb;28(2):759-766. doi: 10.1038/s41380-022-01816-z. Epub 2022 Oct 17.