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Table 1 Summary of studies that employ genome editing technologies to investigate the functions of GWAS loci

From: Editing GWAS: experimental approaches to dissect and exploit disease-associated genetic variation

Trait/disease Index SNP (or causative SNP) Coding or non-coding Target gene Technology Strategy Model Reference (PMID)
Fetal hemogblobin rs1427407 and rs7606173 Regulatory BCL11A TALEN Genomic deletion Mouse erythroleukemia cells and pre-B lymphocyte cells 24115442
Breast cancer rs2981578 Regulatory FGFR2 ZFN Allele substitution MCF7 cells 24265722
Hypertension rs5603 Coding Agtrap, Mthfr, Clcn6, Nppa, Nppb, and Plod1 ZFN Target gene knockout Rat 24006081
Colorectal cancer n.a. Regulatory MYC31 (possible) CRISPR/Cas Genomic deletion HCT116 cells 25268989
Hypertension n.a. n.a. Nr2f2 ZFN Target gene knockout Rat 25687237
Coronary artery disease rs9349379 Regulatory PHACTR1 CRISPR/Cas Genomic deletion Human embryonic stem cells (hESCs) 25838425
Obesity rs1421085   IRX3 and IRX5 CRISPR/Cas Allele substitution Human primary adipocytes 26287746
Prostate cancer rs339331 Regulatory RFX6 TALEN Allele substitution 22Rv1 cells 26398868
Parkinson rs356168 and rs3756054 Regulatory SNCA CRISPR/Cas Allele substitution and genomic deletion hPSCs 27096366
Prostate cancer rs2742624 Regulatory UPK3A CRISPR/Cas Genomic deletion LNCaP cells 27409348
Type 2 diabetes rs7903146 Regulatory ACSL5 CRISPR/Cas Genomic deletion HCT116 cells 27539148
Colorectal cancer rs6983267 Regulatory n.a. CRISPR/Cas Genomic deletion HCT116 cells 26743005
Ankylosing spondylitis rs9283753   PTGER4 CRISPR/Cas Allele substitution Lymphoblastoid cell lines (LCLs) 27259153
Type 2 diabetes N.A. n.a. CDKAL1, KCNQ1, and KCNJ11 CRISPR/Cas Target gene knockout hESCs 27524441
Renal cancer rs35252396   MYC and PVT1 CRISPR/Cas Random indels 786-O renal cancer cells 27774982
Urinary bladder cancer rs8102137 Regulatory CCNE1 CRISPR/Cas Random indels 5637 cells 27514407
Serum acylcarnitine level rs113569197 Coding SLC22A1 CRISPR/Cas Allele substitution Huh7 cells 28942964
Thrombosis rs1039084 Coding STXBP5 CRISPR/Cas Allele substitution Mice 28062498
Schizophrenia rs1198588 Regulatory MIR137 CRISPR/Cas Allele substitution hiPSCs 28803920
Cardiac QT-interval 19bp indel polymorphism Regulatory Rffl-lnc1 CRISPR/Cas Random indels and allele substitution Rat 28827789
Vascular diseases rs9349379 Regulatory EDN1 CRISPR/Cas Allele substitution and genomic deletion iPSCs 28753427
Basophil production rs78744187 Regulatory CEBPA CRISPR/Cas Genomic deletion HSPCs 28031487
Hypertension rs16998073 Regulatory ANTXR2 CRISPR/Cas Target gene knockout Rat 28077422
Blood lipid level rs2277862, rs10889356, rs10889356 and rs10872142 Regulatory CPNE1 and ERGIC3 CRISPR/Cas Genomic deletion, CRISPRi and allele substitution hiPSCs, HepG2 and HEK293T cellls and Mice 28388432
Bicuspid aortic valve rs6601627 and p.S377G (GATA4) Regulatory and coding GATA4 CRISPR/Cas Target gene knockout hiPSCs 28541271
Colorectal cancer rs6983267 Regulatory n.a. CRISPR/Cas Allele substitution HCT-116 cells 29118424
Type 2 diabetes rs780094, rs780095 and rs780096 Regulatory GCKR CRISPR/Cas CRISPRa HepG2 cells 28683826
Breast cancer prevention rs9940645 Regulatory ZNF423 CRISPR/Cas Allele substitution ZR75-1 cells and xenograft model 28821270
Red blood cell hydration and malaria susceptibility rs10751452 Regulatory ATP2B4 CRISPR/Cas Genomic deletion HUDEP-2 and HEK293T cells 28714864
Breast cancer and leukemia rs11055880 and rs12142375 Regulatory ATF7IP, PDE4B CRISPR/Cas CRISPRi HEK293T cells 29061142
Prostate cancer n.a. Regulatory HOXA13, HOTTIP CRISPR/Cas Genomic deletion RWPE-1 cells 29117547
Pediatric chronic kidney disease n.a. Coding GREB1L CRISPR/Cas Target gene knockout Zebrafish 29100090
Height rs9920291 Regulatory CHSY1 CRISPR/Cas Genomic deletion T/C-28a2 cells 29205154
CKD rs17319721 Regulatory SHROOM3 CRISPR/Cas Allele substitution HEK293T cells 29476007
Osteoporosis rs6426749 Regulatory LINC00339 CRISPR/Cas Genomic deletion and CRISPRi HEK293T and hFOB1.19 cells 29706346
Prostate cancer rs11672691 Regulatory PCAT19 and CEACAM21 CRISPR/Cas Allele substitution and CRISPRi/a 22Rv1 cells 30033361
Osteoporosis rs9533090 Regulatory RANKL CRISPR/Cas Genomic deletion U2-OS cell line 29528523
Eyebrow thickness rs1345417 and rs12651896 Regulatory SOX2 and FOXD1 CRISPR/Cas Allele substitution and genomic deletion A375 cells 30248107
Idiopathic pulmonary fibrosis rs2076295 Regulatory DSP CRISPR/Cas CRISPRi/a A549 cells 29924937
Prostate cancer rs12144978 and rs4919742 Regulatory KCNN3 and KRT78 CRISPR/Cas Genomic deletion 22Rv1 cells 30296942
Bladder cancer rs710521 Regulatory ΔNTP63 and p63 CRISPR/Cas Genomic deletion 5637 cells 29956121
Coronary artery disease and ischemic stroke rs17114036 Regulatory PLPP3 CRISPR/Cas Genomic deletion and CRISPRi HAECs cells 30429326
Primary biliary bholangitis rs17032850 and rs227361 Regulatory NFKB1 and MANBA CRISPR/Cas Allele substitution Jurkat cell lines 30528300
Hirschsprung disease, or congenital aganglionosis p.G446R (BACE2) Coding BACE2 CRISPR/Cas Target gene knockout and allele substitution hiPSCs 30217742
Chronic obstructive pulmonary disease rs2013701 Regulatory FAM13A CRISPR/Cas Allele substitution 16HBE cells 30079747
Multiple autoimmune diseases rs558245864 Regulatory BLK CRISPR/Cas Random indels LCL HG00146 cells 30478436
Biliary atresia n.a. n.a. GPC1 or ADD3 CRISPR/Cas Target gene knockout iPSCs 30358741
Pulmonary arterial hypertension rs10958403 and rs765727 Regulatory SOX17 CRISPR/Cas CRISPRi hPAECs cells 30527956
Alzheimer's disease n.a. n.a. FERMT2 CRISPR/Cas Target gene knockout fAD and fADcorr iPSCs 30371777
Colon cancer rs6854845 Regulatory CXCLs (CXCL2, 3, 5, 6 and 8), EREG and EPGN CRISPR/Cas Allele substitution HC, HCT-116 and SW-480 cells 31078271
Total cholesterol and low-density lipoprotein cholesterol rs3780181 Regulatory VLDLR and SMARCA2 CRISPR/Cas Genomic deletion HEK293T cells 30445632
coronary artery disease rs8042271 Regulatory MFGE8 and HAPLN3 CRISPR/Cas Genomic deletion Cell model (HuH-7, relevant to CAD) 30861420
Bone mineral density n.a. Regulatory LHFP CRISPR/Cas Target gene knockout Mice 31042701
Osteoarthritis rs4730222 Regulatory HBP1 CRISPR/Cas Allele substitution Saos-2 cells 31164647
Cardiovascular disease rs2366739 and rs1194196 Regulatory CD36 CRISPR/Cas Genomic deletion K562 and Meg-01 cells 31344026
Chronic obstructive pulmonary disease rs1690789 Regulatory TGFB2 CRISPR/Cas Genomic deletion Primary human lung fibroblasts 31343404
Coronary artery disease, blood pressure, and hypertension rs17163363 Regulatory AIDA CRISPR/Cas Genomic deletion TeloHAEC cells 31287004
Ventricular conduction system function rs13165478 and rs13185595 Regulatory HAND1 CRISPR/Cas Allele substitution and genomic deletion Mice 31366290
Neuropsychiatric disorder n.a. Regulatory CDK5RAP3, STRAP and DRD2 CRISPR/Cas Genomic deletion and CRISPRi i3N iPSCs (Excitatory neurons induced from i3N iPSCs) 31367015
Primary open-angle glaucoma n.a. n.a. CAV1 CRISPR/Cas Target gene knockout Trabecular meshwork cells 30916825
Type 2 diabetes n.a. n.a. ABCC5 CRISPR/Cas Target gene knockout Mice 31338999
Schizophrenia Multiple Regulatory FURIN, SNAP91, TSNARE1 and CLCN3 CRISPR/Cas Multiplexing, allele substitution and CRISPRi/a iPSC 31548722
Atrial fibrillation rs2595104 Regulatory PITX2 CRISPR/Cas Genomic deletion Mice 31636200
Age-related hearing loss c.539G > A, p.R180Q (SLC9A3R1) Coding slc9a3r1 CRISPR/Cas Allele substitution Zebrafish 30863428
Crohn's disease rs6651252 Regulatory MYC CRISPR/Cas Genomic deletion and CRISPRi HCT116 and DLD-1 cells 30794691
Autoimmune diseases rs2476601 and rs1893217 Coding and regulatory PTPN22, PTPN2 CRISPR/Cas Target gene knockout Primary human CD4+ T cells. 31722988
Type 2 diabetes rs534870 Regulatory SPRY2 CRISPR/Cas Target gene knockout HepG2 cells 31664995
Pubertal timing n.a. n.a. LIN28B CRISPR/Cas Target gene knockout Zebrafish 31792362
Multiple diseases n.a. Regulatory TNFAIP3 CRISPR/Cas CRISPRi/a Multiple cell lines 2144282
Colon and rectal adenocarcinoma rs11064124 Regulatory CD9 and PLEKHG6 CRISPR/Cas Genomic deletion HCT116 and LoVo cells 31988071
Prostate Cancer rs10993994 Regulatory MSMB and SNHG11 CRISPR/Cas Genomic deletion LNCaP cells 32065238
Polyunsaturated fatty acid metabolism rs953413 Regulatory ELOVL2 CRISPR/Cas Genomic deletion HepG2 cells 31928966
Major depressive disorder rs3101339 and rs2050033 Regulatory NEGR1, MEI1, NHP2L1, CSDC2, and POLR3H CRISPR/Cas Genomic deletion HEK293T cells 32214206
Breast cancer rs1024176 Regulatory XCL1 CRISPR/Cas Genomic deletion, CRISPRi and CRISPRa BT-474 and MDA-MB-231 cells 31904872
Nonsyndromic cleft lip with or without cleft palate rs4791774 Regulatory NTN1 CRISPR/Cas Target gene knockout Zebrafish 31780810
Erythroid Regeneration rs10892563 Regulatory ARHGEF12 CRISPR/Cas Target gene knockout Zebrafish 31467124
Psoriasis rs10979182 Regulatory KLF4 CRISPR/Cas CRISPRa HaCaT cells 32366252
Major depressive disorder rs70959274 Regulatory LINC01360 CRISPR/Cas Genomic deletion HEK293T cells 32193514