rs138213197 remained highly significant in this analysis ( P = 4.2×10 −12 , Table 1 ) and with an effect size substantially greater than that observed through any of the common variants and broadly similar to that previously reported in the literature (OR = 3.88, 95%C.I. 2.64–5.70).
However, while we cannot completely exclude that common variation may contribute to PrCa risk at this locus as data from the ENCODE project suggests some degree of potential functionality for the variants we have identified here, (in particular rs145922598, which remained marginally significant in the conditional regression, is highly conserved, overlaps a DNaseI hypersensitivity site in several cell lines including LNCaP and transcription factor binding sites for FOXA1 and FOXA2 transcription factors ( Table 1 , Figure 1 )); the much stronger evidence for significance for the rare coding variant coupled with the results of our haplotype analyses appear to indicate that this SNP is solely responsible for the detected association signal.