SPOT is designed to provide investigators with a tool for systematically incorporating their specific biological hypotheses into the post-GWAS prioritization process. The testing of biological hypotheses is a reasonable study design, even if there is no clear evidence of a predictive mechanism. While a GWAS is often touted as being ‘hypothesis free’, this is not exactly the case. Typically a GWAS tests only a particular subset of variants, and designs differ from array to array with some arrays taking into account biological information (3,17). Prior to the availability of GWAS technology, researchers tested candidate genes—a logical and reasonable experiment given the available resources whose success or failure moves the field closer to the goal of testing all known variants with acceptable statistical power. Other examples of biological study designs are GWAS using only non-synonymous SNPs (18,19) and exome sequencing (20). One of the advantages of studying variants with clear biological, although possibly not phenotypically causal, consequences, such as missense SNPs as compared to SNPs not in or near genes, is the potential for conducting functional studies such as knockouts in
