from the discovery analysis of the UHS, rs1329568 (S6H and S7H Figs.). D’ values between rs4878712 and rs1329568 are high in EUR (1.0), but of modest statistical significance, and limited in AFR (0.22) (S8A and S9A Figs.). Their r2 values that suggest no correlation are likely constrained by dissimilar allele frequencies [39] (S8B and S9B Figs.). However, examining the haplotypes of the top discovery and top replication SNPs shows the strongest protective effect in the GG haplotype relative to the high risk AT haplotype, with a meta-analysis P-value (P = 5.44x10-8) nearly an order of magnitude smaller than the meta-analysis of rs4878712 alone. These results suggest that these SNPs may be tapping into a shared haplotype with a causal variant, representing the same signal. See S4 Table for rs4878712-rs1329568 haplotype analyses by cohort, ancestry, and overall.
