It is worth noting that the putative causal locus within the PHF3-PTP4A1 region may not be identical to the risk markers implicated in the current study, and therefore, may need to be identified by sequencing. First, none of the risk SNPs presented here were non-synonymous. Rather, they appear to have implications for risk and function by virtue of their being in LD with a putative causal locus and/or due to their location in regulatory regions (e.g., enhancer elements) that may in turn regulate transcription of the causal locus. Second, the SNPs employed by GWAS are common, but not rare, variants. Numerous studies have shown that many gene-disease associations are not due to a single common variant, but rather due to a constellation of more rare, regionally concentrated, disease-causing variants. Thus, the signals of association credited to our common SNPs may be synthetic associations resulting from the contributions of multiple rare SNPs within the PHF3-PTP4A1 region, which need to be identified by sequencing. Third, both PHF3 and PTP4A1 were found to have significant association and functional signals. PHF3 had weaker association
