or depression but not the other (for reviews, see (Gelernter et al., 2009; Levinson, 2006), and some genes – notably those related to monoaminergic neurotransmitters – have been associated with both (for a review, see (Saraceno et al., 2009). Our results are indicative of an additional layer of complexity – the existence of genetic variants predisposing to specifically to comorbidity, but which are not associated with either disorder on its own. We also explored the possibility that the comorbid cases simply represent a more severe subset of the alcohol dependent cases. Among the full COGA GWAS sample, 66% of the total alcohol dependent cases met criteria for an illicit drug dependence (a phenotype known to capture a more severe subset of cases in COGA, (Dick et al., 2007a), as compared to 67% of the comorbid cases. However, the comorbid cases did endorse significantly more alcohol dependence symptoms than cases with alcohol dependence-only in the full EA sample (mean symptom count=5.8 and 5.3, respectively; p<0.01); additional analyses indicate that the male portion of the sample drove this difference. Thus, it is possible that some of our results are attributable to a slightly more severe level of alcohol dependence. We also note
