A potentially useful gene annotation is whether a genetic variant leads to changes in RNA abundance or structure. This so-called expression QTL approach is in its early stages, but refinement and larger studies could give investigators a useful set of initial hypotheses should an associated region be shown to alter messenger RNA for a nearby gene. These data can also be used to answer a crucial question – to what gene does an associated SNP “belong”? Investigators usually assume that a SNP exerts its immediate effect on a gene it is in or near. In general, this assumption may be reasonable, but there are examples where this assumption is incorrect (e.g., lactase persistence is due to MCM6 intronic variation, ~14kb from the lactase gene). Moreover, 23% of GWAS hits are >20 kb from known genes. Fascinating examples include the 8q24 “gene desert” (30–500 kb from MYC) that is robustly associated with multiple different cancers and a 5p14 region with replicated associations with autism but ~1 Mb from the nearest gene.
