Browsing by Subject "COGA"

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    A Developmentally-Informative Genome-wide Association Study of Alcohol Use Frequency
    (Springer, 2024) Thomas, Nathaniel S.; Gillespie, Nathan A.; Chan, Grace; Edenberg, Howard J.; Kamarajan, Chella; I-Chun Kuo, Sally; Miller, Alex P.; Nurnberger, John I., Jr.; Tischfield, Jay; Dick, Danielle M.; Salvatore, Jessica E.; Medical and Molecular Genetics, School of Medicine
    Contemporary genome-wide association study (GWAS) methods typically do not account for variability in genetic effects throughout development. We applied genomic structural equation modeling to combine developmentally-informative phenotype data and GWAS to create polygenic scores (PGS) for alcohol use frequency that are specific to developmental stage. Longitudinal cohort studies targeted for gene-identification analyses include the Collaborative Study on the Genetics of Alcoholism (adolescence n = 1,118, early adulthood n = 2,762, adulthood n = 5,255), the National Longitudinal Study of Adolescent to Adult Health (adolescence n = 3,089, early adulthood n = 3,993, adulthood n = 5,149), and the Avon Longitudinal Study of Parents and Children (ALSPAC; adolescence n = 5,382, early adulthood n = 3,613). PGS validation analyses were conducted in the COGA sample using an alternate version of the discovery analysis with COGA removed. Results suggest that genetic liability for alcohol use frequency in adolescence may be distinct from genetic liability for alcohol use frequency later in developmental periods. The age-specific PGS predicts an increase of 4 drinking days per year per PGS standard deviation when modeled separately from the common factor PGS in adulthood. The current work was underpowered at all steps of the analysis plan. Though small sample sizes and low statistical power limit the substantive conclusions that can be drawn regarding these research questions, this work provides a foundation for future genetic studies of developmental variability in the genetic underpinnings of alcohol use behaviors and genetically-informed, age-matched phenotype prediction.
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    ssociations of Parental Alcohol Use Disorders and Parental Separation with Offspring Initiation of Alcohol, Cigarette, and Cannabis Use and Sexual Debut in High-Risk Families
    (Wiley, 2017) McCutcheon, Vivia V.; Agrawal, Arpana; Kuo, Sally I-Chun; Su, Jinni; Dick, Danielle M.; Meyers, Jacquelyn L.; Edenberg, Howard J.; Nurnberger, John I.; Kramer, John R.; Kuperman, Samuel; Schuckit, Marc A.; Hesselbrock, Victor M.; Brooks, Andrew; Porjesz, Bernice; Bucholz, Kathleen K.; Department of Biochemistry and Molecular Biology, School of Medicine
    Background and Aims Parental alcohol use disorders (AUDs) and parental separation are associated with increased risk for early use of alcohol in offspring, but whether they increase risks for early use of other substances and for early sexual debut is under-studied. We focused on associations of parental AUDs and parental separation with substance initiation and sexual debut to (1) test the strength of the associations of parental AUDs and parental separation with time to initiation (age in years) of alcohol, tobacco and cannabis use and sexual debut and (2) compare the strength of association of parental AUD and parental separation with initiation. Design Prospective adolescent and young adult cohort of a high-risk family study, the Collaborative Study on the Genetics of Alcoholism (COGA). Setting Six sites in the United States. Participants A total of 3257 offspring (aged 14–33 years) first assessed in 2004 and sought for interview approximately every 2 years thereafter; 1945 (59.7%) offspring had a parent with an AUD. Measurements Diagnostic interview data on offspring substance use and sexual debut were based on first report of these experiences. Parental life-time AUD was based on their own self-report when parents were interviewed (1991–2005) for most parents, or on offspring and other family member reports for parents who were not interviewed. Parental separation was based on offspring reports of not living with both biological parents most of the time between ages 12 and 17 years. Findings Parental AUDs were associated with increased hazards for all outcomes, with cumulative hazards ranging from 1.19 to 2.71. Parental separation was also an independent and consistent predictor of early substance use and sexual debut, with hazards ranging from 1.19 to 2.34. The strength of association of parental separation with substance initiation was equal to that of having two AUD-affected parents, and its association with sexual debut was stronger than the association of parental AUD in one or both parents. Conclusions Parental alcohol use disorders (AUDs) and parental separation are independent and consistent predictors of increased risk for early alcohol, tobacco and cannabis use and sexual debut in offspring from families with a high risk of parental AUDs.