The third susceptibility region for AD+DD occurred at exon 12 of NCAM1 (Table 6); this association was only observed in the family sample. In the case-control sample, we detected a globally significant 3-SNP haplotype (p = 0.015, Table 2), but no specific individual associated haplotype was found. In the family sample, there was evidence for risk (G-A-A) or protective (T-C-A) alleles in the haplotype N8-N10 (Table 6, p = 0.016 ~ 0.0029), located around exon 12 of NCAM1. All of the protective haplotypes contained the same nucleotides at the corresponding SNP loci, consistent with tagging of the same marker locus, and all had the “C” nucleotide in SNP-N9. The risk haplotype N8-N10 of the “G-A-A” allele (p = 0.0036) had a haplotype frequency (12%) that was lower than those of several protective haplotypes (22% ~ 42%) in this family sample.
