It is worth noting that the “causal” variants may not be identical to the “risk” markers, which is actually a common limitation of most association studies. There were other reasons for this inconsistency between the “causal” variants and the “risk” markers implicated in the current study. First, none of the risk SNPs presented here were non-synonymous. Rather, they appeared to have implications for risk and function by virtue of their being in LD with a putative causal variant and/or due to their location in the regulatory region that may in turn regulated transcription of the causal variant. 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 might be synthetic associations resulting from the contributions of multiple rare SNPs in the IPO11-HTR1A region, which needs to be identified by sequencing. Third, the associations in the European-American discovery cohort, the
