The Impact of Polygenic Risk, Parental Separation, and Parental Relationship Discord on Heavy Episodic Drinking Across Adolescence and Young Adulthood in a High-Risk Sample.

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Authors: Kuo, Sally I-Chun; McCutcheon, Vivia V; Bucholz, Kathleen K; Dick, Danielle M; Aliev, Fazil; Meyers, Jacquelyn L; Brislin, Sarah J; Chan, Grace; Edenberg, Howard J; Kamarajan, Chella; Kramer, John; Kuperman, Samuel; Lai, Dongbing; Plawecki, Martin H; Sartor, Carolyn E; Schuckit, Marc A; Salvatore, Jessica E
Year: 2025
Journal: JAACAP open
PMID: 41367971
DOI: 10.1016/j.jaacop.2025.06.001
PMCID: PMC12684652

#	Section	Preview
0	Method	Participants came from the Collaborative Study on the Genetics of Alcoholism (COGA) prospective…
1	Method	The present study made use of data from European Americans (EA) and African Americans (AA), broad…
2	Method	EA individuals (51% male; mean age = 16.41 years, SD = 3.29 at first assessment) and 894 AA…
3	Method — Measures — Frequency of Heavy Episodic Drinking	Frequency of heavy episodic drinking (HED) was coded from participants’ response to the question,…
4	Method — Measures — Parental Separation	Parental separation was based on participant report of not living with both biological parents for…
5	Method — Measures — Perceptions of Parental Relationship Discord	Participants reported on their perceptions of parental relationship discord using 5 questions. These…
6	Method — Measures — Problematic Alcohol Use Polygenic Scores	A full description of genotyping, data processing, quality control, and imputation is provided in…
7	Method — Measures — Problematic Alcohol Use Polygenic Scores	Genetic risk for problematic alcohol use was indexed by constructing genome-wide polygenic scores…
8	Method — Measures — Problematic Alcohol Use Polygenic Scores	genetically similar to reference populations from Africa (ie, AA)36 (COGA sample removed). Because…
9	Method — Analytic Plan	We ran a series of multilevel linear mixed models (MLM) to examine the associations between…
10	Method — Analytic Plan	We used age as the metric of time, and polynomial age terms (ie, linear, quadratic) were included to…
11	Method — Analytic Plan	We conducted analyses in 3 stages. We first determined the longitudinal course of heavy episodic…
12	Method — Analytic Plan	over time? Prior to running the focal analyses, all continuous predictors were centered at their…
13	Method — Analytic Plan	To account for differences in patterns of drinking and broad sociocultural factors,21 focal analyses…
14	Results — Descriptive Statistics	Table 1 summarizes descriptive statistics for the key study variables, separately for EA and AA. In…
15	Results — Descriptive Statistics	and African American ParticipantsEAAAMean (SD) or %Mean (SD) or %Participants, n1,761894Sex,…
16	Results — Linear Mixed Models of the Longitudinal Course of Heavy Episodic Drinking	Figure 1 presents the mean for frequency of HED across the age range by sex, separately for EA and…
17	Results — Analyses Predicting Intercept, Slope, and Quadratic Curvature of the Longitudinal Course of Heavy Episodic Drinking	Table 3, Table 4 present the results from the main effects multilevel growth models of HED as a…
18	Results — Analyses Predicting Intercept, Slope, and Quadratic Curvature of the Longitudinal Course of Heavy Episodic Drinking	S0.182[0.128, 0.236]0.176[0.118, 0.234] Q–0.007[–0.009, –0.004]–0.006[–0.009,…
19	Results — Analyses Predicting Intercept, Slope, and Quadratic Curvature of the Longitudinal Course of Heavy Episodic Drinking	Q–0.002[–0.006, 0.001]–0.001[–0.004, 0.003]PGSPAU I0.012[–0.108, 0.131]0.012[–0.120,…

Name	Type
1000 Genomes Project	cohort
AA	cohort
AA sample	cohort
adolescent heavy drinking local	phenotype
adolescent participants	cohort
adolescents	cohort
African American	cohort
African American (AA) Sample local	cohort
African-like group local	cohort
African-Like Sample local	cohort
Age at first assessment	phenotype
age at initiation of regular drinking local	phenotype
Age at initiation of regular drinking local	phenotype
age at last assessment	phenotype
alcohol	phenotype
Alcohol Initiation	phenotype
alcohol-related behaviors	phenotype
Alcohol Use Disorder	phenotype
AUD	phenotype
baseline assessment	cohort
Black females	cohort
change over time local	phenotype
children’s adjustment local	phenotype
Collaborative Study on the Genetics of Alcoholism (COGA)	cohort
discrimination	phenotype
EA	cohort
EA participants	cohort
early initiation	phenotype
EA sample	cohort
European American (EA) Sample local	cohort
European ancestry	cohort
European-like group local	cohort
familial dysfunction local	phenotype
Familial dysfunction local	phenotype
familial stressors local	phenotype
Familial stressors local	phenotype
family conflict	phenotype
frequency of HED local	phenotype
heavy drinking	phenotype
HED	phenotype
High-risk longitudinal sample local	cohort
high-risk sample	cohort
High-risk sample enriched for familial risk of alcohol use disorder local	cohort
Household chaos local	phenotype
initial status local	phenotype
Number of assessments local	phenotype
offspring	cohort
parental alcoholism	phenotype
parental divorce/separation	phenotype
parental education	phenotype
parental relationship discord	phenotype
Parental separation and discord local	phenotype
parenting	phenotype
participants	cohort
PGSPAU local	phenotype
PGSPAU local	variant
Polygenic predisposition for problematic alcohol use local	variant
polygenic risk score	cohort
problematic alcohol use	phenotype
Problematic Alcohol Use Polygenic Score local	drug
Problematic Alcohol Use Polygenic Score (PGSPAU) local	phenotype
problematic alcohol use polygenic scores local	phenotype
PRS-CS	drug
self-identified race local	phenotype
Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) Interview local	cohort
sex	phenotype
Sex, female local	phenotype
single-parent household local	phenotype
Single-parent households local	phenotype
systemic stressors local	phenotype
White girls local	cohort
young adults	cohort

Citation	PMID	DOI	Status
Alvanzo, A.A. et al., Drug Alcohol Depend, 2011, Race/ethnicity and sex differences in progression from drinking initiation to the development of alcohol dependence	21652154	10.1016/j.drugalcdep.2011.04.024	Cited
Amato, P.R. et al., Am Sociol Rev, 2001, The effects of divorce and marital discord on adult children’s psychological well-being	—	10.2307/3088878	Cited
Amato, P.R. et al., J Marriage Fam, 1991, Parental divorce and adult well-being: a meta-analysis	—	10.2307/353132	Cited
Arkes, J., Subst Use Misuse, 2013, The temporal effects of parental divorce on youth substance use	23363082	10.3109/10826084.2012.755703	Cited
Auersperg, F. et al., J Psychiatr Res, 2019, Long-term effects of parental divorce on mental health—a meta-analysis	31622869	10.1016/j.jpsychires.2019.09.011	Cited
Bates, D. et al., J Stat Softw, 2015, Fitting linear mixed-effects models using lme4	—	10.18637/jss.v067.i01	Cited
Bing, N.M. et al., J Divorce Remarriage, 2009, Comparing the effects of amount of conflict on children's adjustment following parental divorce	—	10.1080/10502550902717699	Cited
Brand, J.E. et al., Proc Natl Acad Sci, 2019, Parental divorce is not uniformly disruptive to children’s educational attainment	30914460	10.1073/pnas.1813049116	Cited
Bucholz, K.K. et al., Alcohol Clin Exp Res, 2017, Comparison of parent, peer, psychiatric, and cannabis use influences across stages of offspring alcohol involvement: evidence from the COGA prospective study	28073157	10.1111/acer.13293	Primary
Bucholz, K.K. et al., J Stud Alcohol, 1994, A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA	8189735	10.15288/jsa.1994.55.149	Primary
Cardon, L.R. et al., Lancet, 2003, Population stratification and spurious allelic association	12598158	10.1016/S0140-6736(03)12520-2	Cited
Cichy, K.E. et al., J Marriage Fam, 2012, Racial differences in exposure and reactivity to daily family stressors	23543937	10.1111/j.1741-3737.2012.00971.x	Cited
Dick, D.M. et al., Genes Brain Behav, 2023, The Collaborative Study on the Genetics of Alcoholism: sample and clinical data	37581339	10.1111/gbb.12860	Primary
Gager, C.T. et al., Marriage Fam Rev, 2016, Conflict or divorce? Does Parental conflict and/or divorce increase the likelihood of adult children's cohabiting and marital dissolution?	—	10.1080/01494929.2015.1095267	Cited
Genomes Project Consortium, Nature, 2015, A global reference for human genetic variation	26432245	10.1038/nature15393	Cited
Giano, Z. et al., BMC Public Health, 2020, The frequencies and disparities of adverse childhood experiences in the U.S	32907569	10.1186/s12889-020-09411-z	Cited
Hussong, A.M. et al., J Abnorm Child Psychol, 1998, Pathways of risk for accelerated heavy alcohol use among adolescent children of alcoholic parents	9915652	10.1023/a:1022699701996	Cited
Huurre, T. et al., Eur Arch Psychiatry Clin Neurosci, 2006, Long-term psychosocial effects of parental divorce	16502211	10.1007/s00406-006-0641-y	Cited
Huurre, T. et al., Soc Psychiatry Psychiatr Epidemiol, 2010, Adolescent risk factors for excessive alcohol use at age 32 years. A 16-year prospective follow-up study	19363578	10.1007/s00127-009-0048-y	Cited
Jackson, K.M. et al., Psychol Addict Behav, 2016, Parental divorce and initiation of alcohol use in early adolescence	27322803	10.1037/adb0000164	Cited
Johnston, L.D. et al., 2019	—	—	—
Kendler, K.S. et al., Arch Gen Psychiatry, 2008, Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood	18519825	10.1001/archpsyc.65.6.674	Cited
Kuo, S.I. et al., Alcoholism, 2023, Association of parental divorce, discord, and polygenic risk with children's alcohol initiation and lifetime risk for alcohol use disorder	36807915	10.1111/acer.15042	Primary
Lai, D. et al., Genes Brain Behav, 2019, Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria	31090166	10.1111/gbb.12579	Primary
Lansford, J.E., Perspect Psychol Sci, 2009, Parental divorce and children's adjustment	26158941	10.1111/j.1745-6924.2009.01114.x	Cited
Li, J.J. et al., Alcoholism, 2017, The impact of peer substance use and polygenic risk on trajectories of heavy episodic drinking across adolescence and emerging adulthood	27991676	10.1111/acer.13282	Primary
Martin, A.R. et al., Nat Genet, 2019, Clinical use of current polygenic risk scores may exacerbate health disparities	30926966	10.1038/s41588-019-0379-x	Cited
McCutcheon, V.V. et al., Addiction, 2018, Associations of parental alcohol use disorders and parental separation with offspring initiation of alcohol, cigarette and cannabis use and sexual debut in high-risk families	28804966	10.1111/add.14003	Primary
McNeish, D. et al., Behav Res Methods, 2018, Differentiating between mixed-effects and latent-curve approaches to growth modeling	29067672	10.3758/s13428-017-0976-5	Cited
National Academies of Sciences, Engineering, and Medicine; Division of Behavioral and Social Sciences and Education; Health and Medicine Division, 2023	36989389	—	Cited
Peterson, C. et al., JAMA Network Open, 2023, Economic burden of health conditions associated with adverse childhood experiences among US adults	38055277	10.1001/jamanetworkopen.2023.46323	Cited
Plomin, R., 2019	—	—	—
Price, A.L. et al., Nat Genet, 2006, Principal components analysis corrects for stratification in genome-wide association studies	16862161	10.1038/ng1847	Cited
R Foundation for Statistical Computing, 2019, R: a language and environment for statistical computing. R Foundation for Statistical Computing	—	—	—
Raley, R.K. et al., The Future of Children/Center for the Future of Children, the David and Lucile Packard Foundation, 2015, The growing racial and ethnic divide in US marriage patterns	27134512	10.1353/foc.2015.0014	Cited
Ruan, Y. et al., Nat Genet, 2022, Improving polygenic prediction in ancestrally diverse populations	35513724	10.1038/s41588-022-01054-7	Cited
Salvatore, J.E. et al., Addiction, 2017, Alcohol use disorder and divorce: evidence for a genetic correlation in a population-based Swedish sample	27981669	10.1111/add.13719	Cited
Salvatore, J.E. et al., J Studies Alcohol Drugs, 2023, Parental divorce and trajectories of alcohol consumption in men: a genetically informative perspective	37306369	10.15288/jsad.23-00033	Cited
Sartor, C.E. et al., Addiction, 2007, The role of childhood risk factors in initiation of alcohol use and progression to alcohol dependence	17222275	10.1111/j.1360-0443.2006.01661.x	Cited
Sartor, C.E. et al., Soc Psychiatry Psychiatr Epidemiol, 2018, The relationship between childhood trauma and alcohol use initiation in Black and White adolescent girls: considering socioeconomic status and neighborhood factors	29151173	10.1007/s00127-017-1461-2	Cited
Shanahan, M.J. et al., J Gerontol Series B, 2005, Social context in gene–environment interactions: retrospect and prospect	15863711	10.1093/geronb/60.Special_Issue_1.65	Cited
Sudhinaraset, M. et al., Alcohol Res, 2016, Social and cultural contexts of alcohol use	27159810	10.35946/arcr.v38.1.05	Cited
Thomas, N.S. et al., Mol Psychiatry, 2023, Genetic nurture effects for alcohol use disorder	36253439	10.1038/s41380-022-01816-z	Primary
Thompson, R.G. et al., Drug Alcohol Depend, 2008, Childhood or adolescent parental divorce/separation, parental history of alcohol problems, and offspring lifetime alcohol dependence	18757141	10.1016/j.drugalcdep.2008.06.011	Cited
Thompson, R.G. et al., J Soc Work Pract Addict, 2013, Parental divorce, maternal-paternal alcohol problems, and adult offspring lifetime alcohol dependence	24678271	10.1080/1533256x.2013.812909	Cited
Verhulst, B. et al., Psychol Med, 2014, The heritability of alcohol use disorders: a meta-analysis of twin and adoption studies	25171596	10.1017/S0033291714002165	Cited
Waldron, M. et al., Drug Alcohol Depend, 2014, Risks for early substance involvement associated with parental alcoholism and parental separation in an adolescent female cohort	24647368	10.1016/j.drugalcdep.2014.02.020	Cited
Werner, K.B. et al., Psychol Addict Behav, 2016, Differences in childhood physical abuse reporting and the association between CPA and alcohol use disorder in European American and African American women	27322801	10.1037/adb0000174	Cited
Young-Wolff, K.C. et al., Clin Psychol Rev, 2011, The influence of gene-environment interactions on alcohol consumption and alcohol use disorders: a comprehensive review	21530476	10.1016/j.cpr.2011.03.005	Cited
Zhou, H. et al., Nat Med, 2023, Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals	38062264	10.1038/s41591-023-02653-5	Cited

The Impact of Polygenic Risk, Parental Separation, and Parental Relationship Discord on Heavy Episodic Drinking Across Adolescence and Young Adulthood in a High-Risk Sample.

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