Excessive alcohol use is the third leading cause of preventable mortality in the United States and one of the top causes of morbidity, with an estimated annual cost of $235 billion. Alcohol is the most commonly used substance in adolescence and is associated with significant negative consequences, including traffic accidents, sexual risk taking, and risk for later alcohol disorders. Alcohol disorders are transmitted intergenerationally, and one in four U.S. children is exposed to parent problem drinking, which contributes to mental and physical health problems that persist into adulthood. To prevent these negative outcomes, interventions in childhood and early adolescence have targeted parenting and family environment influences because of their theoretical role in influencing early drinking and the developmental precursors of alcohol disorders. However, studies are needed to clarify the role of parenting and family environment influences in the context of genetic risk. Failing to consider correlated genetic influences risks mis-estimating parenting and family environment effects and mis-identifying the optimal content and target audiences for interventions. A small and rapidly growing literature tests parenting and family environment effects on offspring alcohol outcomes in the context of geneenvironment correlation and gene-environment interaction, most commonly using candidate gene methods. However, because candidate genes typically explain only small amounts of variance in parenting and alcohol outcomes, these studies often provide weak tests of gene-environment correlation, potentially mis-estimating parenting and family environment effects. The proposed project explores a novel approach to this problem by using an empirically-derived polygenic risk score as an additional control for gene-environment correlation. The project tests parenting and family environment influences on offspring drinking outcomes within the deviance proneness theoretical model. This model hypothesizes that children of alcoholic parents are at risk for a genetically-transmitted vulnerability to behavioral undercontrol, whose effects on alcohol outcomes are exacerbated by parenting that is lacking in support, monitoring, and consistent discipline, and by family environments that are conflictual and disorganized. Based on theory and previous research, we create a polygenic risk score for behavioral undercontrol, with SNPs from candidate genes in dopaminergic, gabergic, and cholinergic systems. Using this theoretically-derived score, the project tests parenting and family environment as mediators and moderators of offspring genetic risk on drinking trajectories. However, in a novel approach, we add an empirically-derived polygenic risk score as an additional control for gene-environment correlation to provide a more rigorous test of parenting and family environment effects. These project goals are accomplished through secondary data analysis of a three-generation, longitudinal, genetically informative, study of the intergenerational transmission of risk for alcohol disorders. The results will better characterize the role of parenting and family environment influences in the intergenerational transmission of alcohol disorders, provide directions for designing family-based prevention programs, and suggest a method to improve future studies of gene-environment interplay in influencing alcohol disorders and their developmental precursors. Relevance Because excessive drinking is one of the leading preventable causes of premature death and disability in the U.S., creating effective prevention programs is an important public health goal. Because one in four U.S. children is exposed to parent problem drinking, minimizing the impact of parent problem drinking on future generations is an important pubic health goal. The proposed project provides a method to improve studies of gene-environment interplay in the development of alcohol disorders and suggests directions for prevention.
|Effective start/end date||9/15/13 → 5/31/17|
- HHS: National Institutes of Health (NIH): $382,329.00