Given that risk variants lie in cell-type-specific enhancer elements, it is critical to utilize a disease-relevant cell type to identify potential enhancer variants. SNPs associated with a particular disease can be compared to enhancer elements to identify cell types whose active enhancers are disproportionately enriched for disease variants. Variant set enrichment is a permutation-based method that compares the enrichment of genetic risk-variant sets within any functional element (such as H3K4me1-marked putative enhancers) to randomly generated matched genetic risk-variant sets [26,38]. This type of analysis provides an unbiased way of evaluating the utility of a cell type for studying the impact of variants on enhancer elements.
