Dataset Information

Association of parental divorce, discord, and polygenic risk with children's alcohol initiation and lifetime risk for alcohol use disorder.

ABSTRACT:

Background

Parental divorce and discord are associated with poorer alcohol-related outcomes for offspring. However, not all children exposed to these stressors develop alcohol problems. Our objective was to test gene-by-environment interaction effects whereby children's genetic risk for alcohol problems modifies the effects of parental divorce and discord to predict alcohol outcomes.

Methods

The sample included European (EA; N = 5608, 47% male, M_age ~ 36 years) and African (AA; N = 1714, 46% female, M_age ~ 33 years) ancestry participants from the Collaborative Study on the Genetics of Alcoholism. Outcomes included age at initiation of regular drinking and lifetime DSM-5 alcohol use disorder (AUD). Predictors included parental divorce, parental relationship discord, and offspring alcohol problems polygenic risk scores (PRS_ALC ). Mixed effects Cox proportional hazard models were used to examine alcohol initiation and generalized linear mixed effects models were used to examine lifetime AUD. Tests of PRS moderation of the effects of parental divorce/relationship discord on alcohol outcomes were examined on multiplicative and additive scales.

Results

Among EA participants, parental divorce, parental discord, and higher PRS_ALC were associated with earlier alcohol initiation and greater lifetime AUD risk. Among AA participants, parental divorce was associated with earlier alcohol initiation and discord was associated with earlier initiation and AUD. PRS_ALC was not associated with either. Parental divorce/discord and PRS_ALC interacted on an additive scale in the EA sample, but no interactions were found in AA participants.

Conclusions

Children's genetic risk for alcohol problems modifies the impact of parental divorce/discord, consistent with an additive model of diathesis-stress interaction, with some differences across ancestry.

SUBMITTER: Kuo SI

PROVIDER: S-EPMC10149624 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Association of parental divorce, discord, and polygenic risk with children's alcohol initiation and lifetime risk for alcohol use disorder.

Kuo Sally I-Chun SI Thomas Nathaniel S NS Aliev Fazil F Bucholz Kathleen K KK Dick Danielle M DM McCutcheon Vivia V VV Meyers Jacquelyn L JL Chan Grace G Kamarajan Chella C Kramer John R JR Hesselbrock Victor V Plawecki Martin H MH Porjesz Bernice B Tischfield Jay J Salvatore Jessica E JE

Alcohol, clinical & experimental research 20230305 4

<h4>Background</h4>Parental divorce and discord are associated with poorer alcohol-related outcomes for offspring. However, not all children exposed to these stressors develop alcohol problems. Our objective was to test gene-by-environment interaction effects whereby children's genetic risk for alcohol problems modifies the effects of parental divorce and discord to predict alcohol outcomes.<h4>Methods</h4>The sample included European (EA; N = 5608, 47% male, M<sub>age</sub> ~ 36 years) and Afr ...[more]

PMID: 36807915

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Project description:BackgroundEarly identification of individuals at high risk for alcohol use disorder (AUD) coupled with prompt interventions could reduce the incidence of AUD. In this study, we investigated whether Polygenic Risk Scores (PRS) can be used to evaluate the risk for AUD and AUD severity (as measured by the number of DSM-5 AUD diagnostic criteria met) and compared their performance with a measure of family history of AUD.MethodsWe studied individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM-5 diagnostic criteria were available for 7203 individuals, of whom 3451 met criteria for DSM-IV alcohol dependence or DSM-5 AUD and 1616 were alcohol-exposed controls aged ≥21 years with no history of AUD or drug dependence. Further, 4842 individuals had a positive first-degree family history of AUD (FH+), 2722 had an unknown family history (FH?), and 336 had a negative family history (FH-). PRS were derived from a meta-analysis of a genome-wide association study of AUD from the Million Veteran Program and scores from the problem subscale of the Alcohol Use Disorders Identification Test in the UK Biobank. We used mixed models to test the association between PRS and risk for AUD and AUD severity.ResultsAUD cases had higher PRS than controls with PRS increasing as the number of DSM-5 diagnostic criteria increased (p-values ≤ 1.85E-05 ) in the full COGA sample, the FH+ subsample, and the FH? subsample. Individuals in the top decile of PRS had odds ratios (OR) for developing AUD of 1.96 (95% CI: 1.54 to 2.51, p-value = 7.57E-08 ) and 1.86 (95% CI: 1.35 to 2.56, p-value = 1.32E-04 ) in the full sample and the FH+ subsample, respectively. These values are comparable to previously reported ORs for a first-degree family history (1.91 to 2.38) estimated from national surveys. PRS were also significantly associated with the DSM-5 AUD diagnostic criterion count in the full sample, the FH+ subsample, and the FH? subsample (p-values ≤6.7E-11 ). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p-values ≤6.8E-10 ).ConclusionsBoth PRS and family history were associated with AUD and AUD severity, indicating that these risk measures assess distinct aspects of liability to AUD traits.

Project description:ImportanceMajor depressive disorder (MDD) and alcohol dependence (AD) are heritable disorders with significant public health burdens, and they are frequently comorbid. Common genetic factors that influence the co-occurrence of MDD and AD have been sought in family, twin, and adoption studies, and results to date have been promising but inconclusive.ObjectiveTo examine whether AD and MDD overlap genetically, using a polygenic score approach.Design, settings, and participantsAssociation analyses were conducted between MDD polygenic risk score (PRS) and AD case-control status in European ancestry samples from 4 independent genome-wide association study (GWAS) data sets: the Collaborative Study on the Genetics of Alcoholism (COGA); the Study of Addiction, Genetics, and Environment (SAGE); the Yale-Penn genetic study of substance dependence; and the National Health and Resilience in Veterans Study (NHRVS). Results from a meta-analysis of MDD (9240 patients with MDD and 9519 controls) from the Psychiatric Genomics Consortium were applied to calculate PRS at thresholds from P < .05 to P ≤ .99 in each AD GWAS data set.Main outcomes and measuresAssociation between MDD PRS and AD.ResultsParticipants analyzed included 788 cases (548 [69.5%] men; mean [SD] age, 38.2 [10.8] years) and 522 controls (151 [28.9.%] men; age [SD], 43.9 [11.6] years) from COGA; 631 cases (333 [52.8%] men; age [SD], 35.0 [7.7] years) and 756 controls (260 [34.4%] male; age [SD] 36.1 [7.7] years) from SAGE; 2135 cases (1375 [64.4%] men; age [SD], 39.4 [11.5] years) and 350 controls (126 [36.0%] men; age [SD], 43.5 [13.9] years) from Yale-Penn; and 317 cases (295 [93.1%] men; age [SD], 59.1 [13.1] years) and 1719 controls (1545 [89.9%] men; age [SD], 64.5 [13.3] years) from NHRVS. Higher MDD PRS was associated with a significantly increased risk of AD in all samples (COGA: best P = 1.7 × 10-6, R2 = 0.026; SAGE: best P = .001, R2 = 0.01; Yale-Penn: best P = .035, R2 = 0.0018; and NHRVS: best P = .004, R2 = 0.0074), with stronger evidence for association after meta-analysis of the 4 samples (best P = 3.3 × 10-9). In analyses adjusted for MDD status in 3 AD GWAS data sets, similar patterns of association were observed (COGA: best P = 7.6 × 10-6, R2 = 0.023; Yale-Penn: best P = .08, R2 = 0.0013; and NHRVS: best P = .006, R2 = 0.0072). After recalculating MDD PRS using MDD GWAS data sets without comorbid MDD-AD cases, significant evidence was observed for an association between the MDD PRS and AD in the meta-analysis of 3 GWAS AD samples without MDD cases (best P = .007).Conclusions and relevanceThese results suggest that shared genetic susceptibility contributes modestly to MDD and AD comorbidity. Individuals with elevated polygenic risk for MDD may also be at risk for AD.

Project description:BackgroundParental separation has been associated with adverse child mental health outcomes in the literature. For school-aged children, joint physical custody (JPC), that is, spending equal time in both parents' homes after a divorce, has been associated with better health and well-being than single care arrangements. Preschool children's well-being in JPC is less studied. The aim of this study was to investigate the association of living arrangements and coparenting quality with mental health in preschool children after parental separation.MethodsThis cross-sectional population-based study includes 12 845 three-year-old children in Sweden. Mental health was measured by parental reports of the Strength and Difficulties Questionnaire and coparenting quality with a four-item scale. The living arrangements of the 642 children in non-intact families were categorised into JPC, living mostly with one parent and living only with one parent.ResultsLinear regression models, adjusted for sociodemographic confounders, showed an association between increased mental health problems and living mostly and only with one parent (B=1.18; 95% CI 0.37 to 2.00, and B=1.20; 95% CI 0.40 to 2.00, respectively), while children in intact families vs JPC did not differ significantly (B=-0.11; 95% CI -0.58 to 0.36). After adjusting the analyses for coparenting quality, differences in child mental health between the post divorce living arrangements were, however, minimal while children in intact families had more mental health problems compared with JPC (B=0.70; 95% CI 0.24 to 1.15). Factorial analysis of covariance revealed that low coparenting quality was more strongly related to mental health problems for children in intact families and JPC compared with children living mostly or only with one parent.ConclusionsThis study suggests that coparenting quality is a key determinant of mental health in preschool children and thus should be targeted in preventive interventions.

Dataset Information

Association of parental divorce, discord, and polygenic risk with children's alcohol initiation and lifetime risk for alcohol use disorder.

Background

Methods

Results

Conclusions

Publications

Association of parental divorce, discord, and polygenic risk with children's alcohol initiation and lifetime risk for alcohol use disorder.

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