Finally, we identified a significant haplotype-specific effect within the 3′UTR for IPO8 (importin 8), a protein that interacts with Argonaute proteins to direct miRNA mediated gene expression regulation [39]. There were nine common 3′UTR haplotypes defined by 13 variants for IPO8. The two haplotype groups defined by the most strongly expression-associated SNPs (two perfectly correlated variants at positions 1147 and 1195 relative to the 3′UTR start) have significantly different (p-value = 9.5×10−4) functional effects. However, unlike LDHC, there remained a substantial amount of variance within the haplotypes defined by alleles at these two SNPs, suggesting other variants may also have a functional role. Alternatively, the data gathered from 3′UTRs were generally noisier than that for promoters (Figure 5 and data not shown), and may not be as sensitive for identifying sequence-specific 3′UTR effects. Due to the increased noise, we repeated the analysis and performed new clone preparations and transfections for a subset of the IPO8 haplotypes. The replicate data also show a significant (p-value = 0.007) difference, in the same direction, between haplotypes defined by their 1147 (or 1195) allele (Figure S12).
