Interestingly, the LD contrast test supports selection at TTC12 exon 3 for AD-only (p-value = 0.00005), and the LD contrast plot shows the difference between cases and controls (see Figure 3C). “One situation when the LD contrast test is particularly powerful is when dissimilar haplotypes (‘yin yang haplotypes’) carry susceptibility. This could either indicate a true heterogeneity of the mechanism, or that they are ‘proxies’ for an unobserved causative mutation or haplotype.” (personal communication from Dr. Dmitri Zaykin, January 12th, 2007). The haplotypes in TTC12 exon 3 in this sample are exactly “yin-yang haplotypes.” Therefore, it is unknown why there was selection at TTC12 exon 3 for AD-only but no evidence for association emerged. Additional studies with large samples are necessary to validate these findings. It should be noted, however, that in studies from COGA, evidence for an association of GABRA2 and CHRM2 previously observed with AD came only from individuals with comorbid DD, with no evidence of association among individuals with AD but no DD (Agrawal et al., 2006; Dick et al., 2007a). We conclude that TTC12 exon 3
