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