Identifying candidate susceptibility genes in regions associated with disease using the proximity of the candidate genes to SNPs in that region may be misleading a lot of the time. For example, from Table S2, for the 3,210 expression traits giving rise to cis eQTLs, only 627 of the corresponding cis eSNPs are located within the corresponding gene region, whereas 1,282 are located downstream of the 3′ untranslated region (UTR) and 1,301 are located upstream of the 5′ UTR. Further, of the cis eSNPs located up- and downstream of the corresponding genes, 490 and 526, respectively, are >100 kb away. That is, greater than 30% of all cis eSNPs fall greater than 100 kb away from the transcription start and stop sites of the corresponding gene. Therefore, at least for expression traits, the nearest SNP rule for inferring genes given an association finding would result in an unacceptably high miss-call rate. Genes with expression values that are strongly associated with variations in DNA provide a different path to elucidate the gene or genes and their respective functions underlying genetic loci associated with disease in a more objective fashion.
