|
INTRODUCTION Elevated rates of childhood trauma, particularly childhood sexual abuse (CSA) or physical abuse (PA) have been reported in studies assessing adults and adolescents presenting for the treatment of alcoholism or drug dependence. Trauma survivors in treatment have increased rates of alcohol and drug dependence and other negative outcomes. However, despite highly replicable relationships between trauma and adverse outcomes, establishing the causal role of trauma has proved difficult. General population studies have attempted to control for possible confounding by family background factors (e.g., parental alcoholism) that are associated with risks for both the trauma and its sequelae by identifying a number of these factors and then entering them into regression models. Recent investigation in twins, which have used non-abused co-twins to control for family background, have confirmed associations with negative outcomes and suggested that prior statistical controls were overly conservative. This project undertakes a follow-up interview of a unique cohort of 3607 individuals constituting the sample for a funded Genome-wide Association Study (GWAS) of alcohol dependence (1799 alcohol dependent cases and 1808 controls, with about half deriving from large sib-ships), over the next 5 to 7 years. The sample is unique in two important respects: it comprises individuals who were ascertained through a series of surveys of community-based rather than clinically ascertained samples, specifically through surveys of the Australian twin panel; and it is comprised of a cohort of individuals who grew up at a time when divorce laws in Australia were very restrictive. Even though parental alcoholism was a potent predictor of parental divorce, the vast majority of those reporting parental alcoholism (85%) grew up with both biologic parents through age 16. We are thus well positioned to document interactions of SNP genotype effects with environmental exposures associated with parental alcoholism. Animal studies and human studies have demonstrated the importance of genotype x environment interactions contributing to complex traits, but have usually been implemented in the context of candidate gene studies, rather than in the context of a GWAS. This study will collect detailed information on environmental stressors which, in combination with the previously funded GWAS will enable a program of data analysis to examine genotype x environment interactions contributing to our primary dependent variable, a quantitative alcohol consumption factor. |