Genome-wide association study (GWAS) has been a popular approach to identify trait associated genetic variants so-called single nucleotide polymorphisms (SNPs). GWASs compare the allele frequencies of case groups (i.e., disease groups) and control groups (i.e., normal groups) of study participants to identify the SNPs that are significantly more enriched in case groups than control groups. If an allele is significantly more frequent in case groups, the allele is said to be a disease-associated allele, or a trait-associated SNP (TAS). In theory, TASs are considered to reside near sites of actual disease-causing mutations in genomes. Interestingly, most of the TASs detected by GWASs have been mapped to intron regions rather than exonic or nonsysnonymous sites (Fig. 1A) [4368]. The statistical significance of this finding was proven by a comparison of the proportion of intronic SNPs mapped by all SNPs obtained from 'v dbSNP 142' after subtracting the TASs (i.e., all SNPs minus TASs) and the proportion of intronic TASs (p<0.01) (Fig. 1B). Investigation of the functional implication of these intron-TASs will thus be an important research subject in the future.
