Several computational programs are currently available to integrate chromatin landscapes with GWAS risk variants to identify candidate regulatory SNPs and evaluate their disease-causing potential. These include IGR [38], RegulomeDB [51], HaploReg [52], FunciSNP [53] and FunSeq [54]. These programs are particularly useful for prioritizing SNPs for functional analyses, which may include transcription factor ChIP or electrophoretic mobility shift assays to test whether a given SNP influences a transcription factor’s ability to bind to the enhancer, and in vitro and in vivo gene reporter assays to test the SNP’s effect on enhancer activity. Additionally, allele-specific expression can be utilized to quantify the impact of enhancer variants within a specific cell type. Finally, DNA editing strategies involving CRISPR/Cas9-based methods can be employed to evaluate the effect of a variant. Following the identification of a functional enhancer variant, the next major challenge is to identify its target and to test the effect of the SNP(s) on target transcript levels. Many enhancer elements are located within 100 kilobases (kb) of the genes that they regulate, but can also be located more than a megabase
