This is the first GWAS to our knowledge that examines each individual criterion of the DSM-IV AD diagnosis as well as phenotypes defined by the probability of latent class assignment. As such, it is the first association study demonstrating genome-wide significance with one of the DSM-IV AD criteria as well as with the phenotype derived from the probability of membership in the high-risk class. This suggests that characterizing more homogeneous subgroups of individuals, defined either by a specific AD criterion or by the probability of belonging to a latent class, increased the power to detect genetic association relative to the diagnosis of AD, a particularly heterogeneous phenotype. For example, estimated power was equivalent for the two phenotypes DSM-IV and persistent desire/inability to cut down, yet one of the strongest association results was with the persistent desire/inability to cut down, p=7.3 × 10−8, while there was modest evidence of association with DSM-IV (p=1.5 × 10−5, Supplementaltal Table 1).
