Offspring of Twins: G,E and GxE Risks for Alcoholism

Palo Alto Institute For Res &Edu, Inc., Palo Alto CA

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Abstract

DESCRIPTION (provided by applicant): The goal of this renewal application is the continued study of the development and course of alcoholism among an unusually well characterized sample of young adults at differing degrees of genetic and environmental risk for Alcohol Use Disorders (AUD). Our approach is distinguished by two significant design characteristics: (1) use of the powerful children of twins (COT) design involving twins in the parent generation who are concordant or discordant for alcohol dependence (and control pairs) as well as their offspring and the mothers of the offspring, and (2) use of a prospective design allowing for the description of offspring development from adolescence through the early thirties. In our initial study (T1), a sample of male twins and their family members were selected from the Vietnam Era Twin Registry and were administered a comprehensive psychiatric and psychosocial interview by telephone; offspring were reassessed two years later (T2). Evidence from the initial study demonstrated a GxE interaction effect in the emergence of alcoholism; specifically, offspring at both high genetic and high environmental risk (the biological and rearing father being alcohol dependent) were significantly more likely to exhibit Alcohol Abuse and Alcohol Dependence than were offspring at high genetic risk only (without the environmental risk since the biological and rearing father was nonaffected but his MZ cotwin was alcohol dependent). This effect, indicating he importance of family environmental influences on offspring outcome, has less often been reported in studies using the classical twin design or adoption design. It is the ability of the COT design to better untangle genetic and environmental influences that underscores the importance of current findings. Therefore, in the proposed continuation, we will conduct a T3 and T4 assessment on offspring at two year intervals as they move through their period of highest risk for AUD, and we emphasize a longitudinal/developmental perspective in order to obtain stronger evidence for prospective relations involving predictor variables and offspring outcomes; to determine the persistence of effects over time; to identify later stage influences that interact with initial stage influences in accounting for variation in drinking and nondrinking outcomes; and to examine different alcohol use trajectories characterizing the young adult years and how these differ by risk group. Both risk and protective factors contributing to offspring development, psychiatric, and psychosocial outcomes have been shown to originate in genetic, and environmental influences and their interplay. The proposed study promises further elucidation of genetic precursors and environmental risk factors and their interaction thus advancing understanding of the development and treatment of alcoholism and related disorders.