history of SUD support a causal influence of prenatal exposure on offspring substance use (Ernst et al., 2001, Glantz and Chambers, 2006), whereas family-based, quasi-experimental designs indicate that familial background factors explain this association (D’Onofrio et al., 2012, Ellingson et al., 2012). Studies controlling for a family history of SUD implicate a causal influence of prenatal alcohol exposure on offspring substance use problems (Baer et al., 1998, Baer et al., 2003), but this association has not been examined within a family-based research design. To our knowledge, neither the effect of prenatal alcohol nor cigarette exposure in the context of ultra-high familial risk has been examined. The assessment of offspring outcomes in individuals with similarly high genetic loading for SUD but varying prenatal exposures provides a unique opportunity to disentangle the impact of these factors on offspring outcomes. Previous studies utilizing offspring at ultra-high familial risk for alcohol dependence have yielded important findings on the association between prenatal exposures and adolescent psychiatric disorders (Hill et al., 2000) and body mass index (BMI) (Hill et al., 2005). The present results extend the previous observations by relating prenatal exposure and familial risk to offspring outcome now that the sample has now reach young
