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Table 2 Functional enhancer studies of GWAS risk loci

From: Enhancer variants: evaluating functions in common disease

Disease/trait Reference Lead SNP Proposed functional SNP Gene target How gene target was selected Cell type Data supporting SNP enhancer function
Blond hair color Guenther et al.[33] rs12821256 rs12821256 KITLG Phenotype in mouse model Developing hair follicles, HaCaT karatinocyte cell line Allele-specific luciferase activity, allele-specific ChIP, effect of SNP on mouse phenotype
Breast cancer Cowper-Sal lari et al.[38] rs4784227 rs4784227 TOX3 3C MCF7 Binding motif disruption, allele-specific ChIP, allele-specific 3C, allele-specific expression, eQTL
Colorectal cancer Pomerantz et al.[34] rs6983267 rs6983267 c-MYC 3C Colo205 and LS174T Allele-specific luciferase activity, allele-specific ChIP
Colorectal cancer Wright et al.[39] rs6983267 rs6983267 c-MYC 3C DLD1 and HCT116 Allele-specific ChIP, allele-specific expression
Colorectal cancer Tuupanen et al.[36] rs67491583 rs67491583 c-MYC Nearest gene HeLa Binding motif disruption, allele-specific ChIP, allele-specific luciferase activity
Prostate cancer Wasserman et al.[35] rs6983267 rs6983267 c-MYC Nearest gene Prostate tissue (mouse) Allele-specific activity, LacZ enhancer assay (mouse)
Coronary artery disease Harismendy et al.[31] rs10757278 rs10811656/ rs10757278 CDKN2B, CDKN2BAS, IFNA21, MTAP 3C and FISH (IFNA21) HUVEC Binding motif disruption, allele-specific ChIP
Coronary heart disease Miller et al.[29] rs12190287 rs12190287 TCF21 Nearest gene, eQTL gene HCASMC Binding motif disruption, allele-specific luciferase activity, EMSA, allele-specific ChIP and allele-specific expression
Fetal hemoglobin level Bauer et al.[28] rs1427407, rs7606173 rs1427407, rs7606173 BCL11A 3C Primary human erythroblasts Binding motif disruption, allele-specific ChIP, allele-specific expression, LacZ enhancer assay (mouse), deletion by TALEN
Multiple sclerosis Alcina et al.[27] rs658115 rs10877013 FAM119B, AVIL, TSFM, TSPAN31 eQTL LCLs and monocytes Allele-specific luciferase activity, eQTL
Obesity Smemo et al.[30] rs9930506 NA IRX3 4C-seq, 3C, ChIA-PET, Hi-C Whole mouse embryo and adult mouse brain eQTL mapping
Prostate cancer Hazelett et al.[6] rs5945619 rs4907792 NUDT1 Nearest gene, eQTL gene LNCaP Allele-specific luciferase activity, eQTL
Prostate cancer Hazelett et al.[6] rs10486567 rs10486567 JAZF1 Nearest gene LNCaP Allele-specific luciferase activity, binding motif disruption
QT interval Kapoor et al.[32] rs12143842 rs7539120 NOS1AP eQTL gene, genetic association Cardiac tissues Allele-specific luciferase activity, eQTL, enhancer assay (zebrafish embryos)
Restless leg syndrome Spieler et al.[37] rs12469063 rs13469063 MEIS1 PreSTIGE prediction method, ChIA-PET, Hi-C Telencephalon Allele-specific expression of reporter gene in zebrafish, Allele-specific LacZ (mouse), EMSA, binding motif disruption, effect of decreased gene expression on phenotype
Systemic lupus erythematosus Wang et al.[40] rs2230926 rs148314165, rs200820567 TNFAIP3 3C LCLs EMSA, allele-specific luciferase activity, allele-specific 3C
Type 2 diabetes Gaulton et al.[76] rs7903146 rs7903146 TCF7L2 Nearest gene Pancreatic islet cells Allele-specific luciferase activity, allele-specific FAIRE
  1. 3C, chromosome conformation capture; 4C-seq, circular chromosome conformation capture followed by sequencing; ChIA-PET, chromatin interaction analysis by paired-end tag sequencing; ChIP, chromatin immunoprecipitation; EMSA, electrophoretic mobility shift assay; eQTL, expression quantitative trait loci; FAIRE, formaldehyde-assisted isolation of regulatory elements; FISH, fluorescence in situ hybridization; LCLs, lymphoblastoid cell lines; NA, not applicable; SNP, single nucleotide polymorphism.