Another method for disentangling the relation between the direct, causal effects of prenatal exposures and indirect, genetic effects on offspring outcomes is to use samples enriched for a high familial density of alcohol dependence in which offspring carry a much higher genetic risk for substance use problems. This design can provide information on the link between prenatal exposures and offspring outcomes among individuals with high genetic loading for SUD. Accordingly, the current study sought to examine the relative contribution of having a multiplex, familial history of alcohol dependence and prenatal exposure to alcohol and/or cigarettes on offspring smoking and drinking behavior. The goals of the study were: (1) to compare rates of maternal substance use in women varying in family density of alcohol dependence; (2) to determine if prenatal exposure to alcohol and cigarettes would increase offspring use of these substances; and (3) to determine if exposure to these substances would increase the rate of offspring substance use controlling for familial risk. The latter goal was carried out by contrasting exposed and non-exposed offspring within the High-Risk sample. It was
