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 |