Table 5.

Examples of regulatory enrichment analyses of genetic associations.

Class of test	Finding	Computational tools used
Gene set enrichment near associated loci	Regulatory network of five proteins implicated in Kawasaki disease192	Ingenuity Pathway Analysis (closed-source)
	Genes differentially expressed in adipose overlap with genetic associations with obesity193	Microarray analysis of differential expression
	TGF-β pathway, Hedgehog signaling pathway are enriched among height GWAS loci103	GSEA using MAGENTA194, network from text-mining using GRAIL195, known disease genes from OMIM4, eQTL enrichment
Concordance with eQTL results	eQTL prioritization during replication facilitated validation of two Crohn’s disease susceptibility loci196	eQTL enrichment
	GWAS involving immune system show enrichment for lymphoblastoid eQTL64	eQTL enrichment (RTC64)
Chromatin state enrichment	Many GWAS show enrichment for enhancers in biologically-relevant cell types62	ChromHMM to define discrete chromatin states197 (M.K. and colleagues); enrichment analysis
TF binding site and DNase hypersensitivity enrichment	Many GWAS show enrichment for ENCODE-annotated DNAse and ChIP sites198	Enrichment analysis
	Many GWAS show enrichment for DNAse in biologically-relevant cell types63	Hotspot algorithm to define discrete hypersensitive sites199; enrichment analysis
	FOXA1 and estrogen receptor binding sites are enriched among breast cancer GWAS loci200	Variant Set Enrichment (VSE200)