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. 2023 Feb;28(2):759-766.
doi: 10.1038/s41380-022-01816-z. Epub 2022 Oct 17.

Genetic nurture effects for alcohol use disorder

Nathaniel S Thomas #  1 , Jessica E Salvatore #  2 , Sally I-Chun Kuo  3 , Fazil Aliev  3 , Vivia V McCutcheon  4 , Jacquelyn M Meyers  5 , Kathleen K Bucholz  4 , Sarah J Brislin  3 , Grace Chan  6   7 , Howard J Edenberg  8 , Chella Kamarajan  5 , John R Kramer  7 , Samuel Kuperman  7 , Gayathri Pandey  5 , Martin H Plawecki  9 , Marc A Schuckit  10 , Danielle M Dick  3 ; COGA Collaborators
Collaborators, Affiliations

Genetic nurture effects for alcohol use disorder

Nathaniel S Thomas et al. Mol Psychiatry. 2023 Feb.

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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Conflict of interest statement

Conflict of Interest

None

Figures

Figure 1.
Figure 1.
Illustrative extended nature of nurture model for AUDSx (DSM-5 Alcohol Use Disorder Criterion Count) depicting parental divorce and parental AUDSx as mediators of genetic risk across generations. Paternal and maternal genotypes are partitioned into those that are shared with the offspring (i.e., transmitted paternal and alleles, Tp and Tm, respectively) and those that are not shared with offspring (i.e., nontransmitted paternal and maternal alleles, NTp and NTm, respectively). Parental divorce (Yd), paternal AUDSx (Yp), and maternal AUDSx (Ym) are included as mediators, and the outcome is offspring AUDSx (Yo). Transmitted paternal alleles can have a direct effect on offspring AUDSx (Tp.Yo), or mediated (indirect) effects through paternal AUDSx (Tp.Yp × Yp.Yo) or parental divorce (Tp.Yd × Yd.Yo). Nontransmitted paternal alleles can have indirect effects through paternal AUDSx (NTp.Yp × Yp.Yo) or parental divorce (NTp.Yd × Yd.Yo). Corresponding paths exist for mothers, such that transmitted maternal alleles can have a direct effect on offspring AUDSx (Tm.Yo), or mediated (indirect) effects through maternal AUDSx (Tm.Ym × Ym.Yo) or parental divorce (Tm.Ym × Ym.Yd). Nontransmitted maternal alleles can have indirect effects through maternal AUDSx (NTm.Ym × Ym.Yo) or parental divorce (NTm.Yd × Yd.Yo). All paths are estimated simultaneously.
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