Genetic nurture effects for alcohol use disorder.
paper
Primary
Public
- Authors
- Thomas, Nathaniel S; Salvatore, Jessica E; Kuo, Sally I-Chun; Aliev, Fazil; McCutcheon, Vivia V; Meyers, Jacquelyn M; Bucholz, Kathleen K; Brislin, Sarah J; Chan, Grace; Edenberg, Howard J; Kamarajan, Chella; Kramer, John R; Kuperman, Samuel; Pandey, Gayathri; Plawecki, Martin H; Schuckit, Marc A; Dick, Danielle M; COGA Collaborators
- Year
- 2023
- Journal
- Molecular psychiatry
- PMID
- 36253439
- DOI
- 10.1038/s41380-022-01816-z
- PMCID
- PMC10079179
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 (Nβ=β4806, 51% female) and African ancestry (Nβ=β1960, 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 24βh, 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 (Ξ²β=β-0.018 [-0.026, -0.011]) and intoxication (Ξ²β=β-0.015 [-0.023, -0.008]), greater lifetime maximum drinks (Ξ²β=β0.006 [0.002, 0.01]) and more lifetime AUD criteria (Ξ²β=β0.011 [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.
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 Γ Yp.Yo) or parental divorce (Tp.Yd Γ Yd.Yo). Nontransmitted paternal alleles can have indirect effects through paternal AUDSx (NTp.Yp Γ Yp.Yo) or parental divorce (NTp.Yd Γ 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 Γ Ym.Yo) or parental divorce (Tm.Ym Γ Ym.Yd). Nontransmitted maternal alleles can have indirect effects through maternal AUDSx (NTm.Ym Γ Ym.Yo) or parental divorce (NTm.Yd Γ Yd.Yo). All paths are estimated simultaneously.
β Prev
21β36 of 36
| Name | Type |
|---|---|
| 1000 Genomes Phase III African subsample local | cohort |
| 1000 Genomes Phase III European subsample local | cohort |
| AA | cohort |
| AA families | cohort |
| AA offspring local | cohort |
| AA sample | cohort |
| adoption studies | cohort |
| adverse childhood experiences | phenotype |
| Adverse family experiences local | phenotype |
| African American | cohort |
| African ancestry families local | cohort |
| Age at alcohol initiation local | phenotype |
| age at first intoxication | phenotype |
| age at initiation | phenotype |
| age at intoxication local | phenotype |
| Age at Intoxication local | phenotype |
| age at last assessment | phenotype |
| alcohol | phenotype |
| Alcohol Initiation | phenotype |
| alcohol intoxication | phenotype |
| Alcohol Problems | phenotype |
| alcohol-related outcomes | phenotype |
| alcohol-related phenotypes | phenotype |
| Alcohol Use | phenotype |
| Alcohol Use Disorder | phenotype |
| Alcohol use disorder clinical criteria local | phenotype |
| alcohol use disorders | phenotype |
| ancestry | phenotype |
| ancestry groups | cohort |
| AUD | phenotype |
| AUDIT-P | phenotype |
| baby boomer local | cohort |
| Child AUD clinical criterion counts local | phenotype |
| Child generation local | cohort |
| children | cohort |
| Childrenβs age at first intoxication local | phenotype |
| COGA sample | cohort |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| Community comparison families | cohort |
| DSM-5 AUD | phenotype |
| DSM-IV alcohol dependence | phenotype |
| EA | cohort |
| EA families | cohort |
| EA offspring local | cohort |
| EA participants | cohort |
| Earlier age at first drink local | phenotype |
| Earlier age at initiation local | phenotype |
| EA sample | cohort |
| European ancestry | cohort |
| European ancestry families local | cohort |
| families | cohort |
| generational cohort local | cohort |
| generation X local | cohort |
| Higher substance involvement and misuse local | phenotype |
| high-risk sample | cohort |
| ICD codes local | drug |
| initiation | phenotype |
| intoxication | phenotype |
| Lifetime clinical criteria for alcohol use disorder local | phenotype |
| Maternal age at first intoxication local | phenotype |
| maternal alcohol use behaviors local | phenotype |
| maternal allele (nontransmitted) local | variant |
| maternal allele (transmitted) local | variant |
| Maternal AUD clinical criterion counts local | phenotype |
| Maternal AUDSx local | phenotype |
| maternal Intoxication local | phenotype |
| Maternal MaxDrinks local | phenotype |
| maternal nontransmitted alleles local | variant |
| maxdrinks | phenotype |
| maximum drinks | phenotype |
| Maximum drinks consumed in 24 hours local | phenotype |
| millennial local | cohort |
| Million Veteran Program | cohort |
| nontransmitted alleles local | variant |
| Nontransmitted alleles local | variant |
| nontransmitted maternal allele local | variant |
| Nontransmitted maternal allele local | variant |
| nontransmitted maternal alleles local | variant |
| Nontransmitted maternal alleles local | variant |
| Nontransmitted maternal alleles for alcohol problems local | variant |
| non-transmitted parental alleles local | variant |
| nontransmitted parental alleles local | variant |
| nontransmitted paternal allele local | variant |
| Nontransmitted paternal allele local | variant |
| nontransmitted paternal alleles local | variant |
| Nontransmitted paternal alleles local | variant |
| Nontransmitted paternal alleles for alcohol problems local | variant |
| offspring | cohort |
| offspring alcohol involvement | phenotype |
| offspring alcohol outcomes local | phenotype |
| Offspring alcohol outcomes local | phenotype |
| Offspring alcohol use phenotype local | phenotype |
| offspring AUDSx local | phenotype |
| Offspring AUDSx local | phenotype |
| Offspring birth cohort local | cohort |
| offspring Initiation local | phenotype |
| Offspring Initiation local | phenotype |
| offspring Intoxication local | phenotype |
| Offspring Intoxication local | phenotype |
| offspring Max Drinks local | phenotype |
| Offspring MaxDrinks local | phenotype |
| offspring phenotype local | phenotype |
| Parental alcohol use behaviors local | phenotype |
| Parental alcohol use phenotype local | phenotype |
| parental alcohol use phenotypes local | phenotype |
| parental alleles local | variant |
| Parental AUD clinical criterion counts local | phenotype |
| parental divorce/separation | phenotype |
| Parental marital discord local | phenotype |
| parental monitoring | phenotype |
| parental phenotype local | phenotype |
| Parental polygenic scores local | variant |
| parental relationship discord | phenotype |
| parents | cohort |
| paternal alcohol use behaviors local | phenotype |
| paternal allele (nontransmitted) local | variant |
| paternal allele (transmitted) local | variant |
| Polygenic risk score for alcohol dependence | phenotype |
| probands | cohort |
| Psychiatric Genomics Consortium | cohort |
| sex | phenotype |
| silent local | cohort |
| SSAGA | cohort |
| SSAGA32 local | cohort |
| substance use | phenotype |
| tobacco use | phenotype |
| transmitted alleles local | variant |
| Transmitted alleles local | variant |
| transmitted maternal allele local | variant |
| Transmitted maternal allele local | variant |
| transmitted maternal alleles local | variant |
| Transmitted maternal alleles for alcohol problems local | variant |
| transmitted parental alleles local | variant |
| transmitted paternal allele local | variant |
| Transmitted paternal allele local | variant |
| transmitted paternal alleles local | variant |
| Twin cohort | cohort |
| UK Biobank | cohort |
| UKBiobank local | cohort |
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