the potentially uniquely important information from each linkage distribution block spanning the entire region, showing significance with any marker in either population sample. The haplotype that included this SNP combination was significantly associated in AAs (global, P=.003), EAs (global, P=.02), and the combined sample of families (global, P=.001). The specific haplotype T-T-A was associated with CIP in EAs (P=.01) and AAs (P=.02), and in the pooled sample (P<.001). Haplotype C-A-C was associated with decreased risk of CIP in EAs (P=.01) and AAs (P<.001), and in the total sample (P<.001). These 2 haplotypes account for 86% and 73% of all haplotypes in the EA and AA families, respectively. A third haplotype (C-T-A), which had appreciable frequency in both EAs (6%) and AAs (23%), was also associated with increased risk of CIP. Because both rs9400554 alleles were part of different risk haplotypes, the functional variant is more likely to be closer to the other 2 SNPs. Thus, these results, showing strong evidence for association of the same haplotype to CIP in 2 distinct populations, support the existence of a single causative variant that is most likely located in the MANEA promoter or coding region.
