these data 9. However, assessment of the genomic underpinnings of such heterogeneous groups of individuals would require extremely large sample sizes. The chromosome 8 variant, rs188227250, was uniquely associated with Drinking more than intended (Supplemental Table 7). In epidemiological studies and in COGA (Supplemental Table 2), this criterion is endorsed quite frequently by individuals with AD, and also by those who do not meet criteria for DSM-IV AD and thus, might index lower severity. Indeed, in IRT analyses, this criterion had the lowest difficulty as indicated by the item characteristic curves in Supplemental Figure 7. In contrast, the finding on chromosomes 2 and 15, while GWS for Time spent drinking were also associated with Giving up activities (at nearly GWS for chromosome 15), both highly correlated criteria indicative of high difficulty, and thus, risk for DSM-IV AD 9. In addition to Withdrawal, we previously found these criteria to distinguish a highly heritable high-risk group of individuals at risk for AD from those in both low and moderate-risk groups. Thus, as shown in Supplemental Figure 7, while the chromosome 8 finding potential maps to lower AD severity, the chromosome 2 and 15 findings potentially indicate greater severity. However none of these
