The Encyclopedia of DNA Elements (ENCODE) project has identified a comprehensive map of functional elements and active chromatin marks by advanced techniques such as ChIP-seq, DNase-seq, bisulfate sequencing, chromosome conformation capture and so forth. (15,16). Recent studies showed that disease-associated single-nucleotide polymorphisms (SNPs) detected by GWAS are significantly enriched in the regions that harbor functional elements, such as transcriptional factor binding sites (TFBSs), histone modification marked regions, DNase I hypersensitive sites (DHSs) and expression quantitative trait loci (16–19). Two recently published databases, HaploReg (20) and RegulomeDB (21), have used these regulatory signals and marks to annotate the genetic variants, which offer comprehensive resources on regulatory variation. On the other hand, different functional elements have been reported to function in a tissue/cell type-specific manner. SNPs associated with the same trait are likely to locate in active chromatin marks in the same/relevant cell type (22), implying the possibility of detecting regulatory signals using the chromatin marks of phenotypically relevant cell type. Computational algorithms including ChromHMM (23) and Seaway (24) have been successfully applied to scan different functional elements in the genome. Therefore,
