As we moved our focus in the association analysis from the significant global haplotypes to the specific individual haplotypic associations, additional interesting results were revealed. Overall in TTC12, the risk haplotypes extended from T1 to T9 and covered the whole gene (individual haplotype simulated p-values (pihs) = 0.0094 ~ 0.000015 for the case-control sample; 0.0094 ~ 0.0034 for the family sample; Table 4). In the family sample, all the risk haplotypes shared the same polymorphic nucleotides at the same risk locus, and no risk haplotypes contained markers downstream of SNP T5, which is in TTC12 exon 3. In the case-control sample, more risk haplotypes were identified, and those with >10% difference in haplotype frequency between cases and controls centered around T4-T5, i.e., TTC12 exon 3 as well, and contained two “yin-yang” haplotypes “G-A” or “T-C”. The difference in haplotype frequency (between cases and controls) decreased as the risk haplotype was more distant from TTC12 exon 3.
