Table 1 Prioritized drug targets for POAG
From: Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci
Gene | Mapping criteria | Only VCDR effecta | Drug name | Mechanism of action | Diseases under trial |
|---|---|---|---|---|---|
COL11A1 | Nearest gene/MAGMA, TWAS, eQTL coloc | No | Collagenase clostridium histolyticum, ocriplasmin | Collagen hydrolytic enzyme | Macular degeneration and macular holes, diabetic macular edema, retinal vein occlusion |
CYP26A1 | Nearest gene, TWAS, eQTL coloc | Yes | Talarozole | Cytochrome P450 26A1 inhibitor | Acne, psoriasis, inflammation |
NDUFS3 | MAGMA, TWAS, eQTL coloc | No | Metformin, ME-344 and others | Mitochondrial complex I (NADH dehydrogenase) inhibitor | Stargardt disease, muscular dystrophy, diabetic retinopathy, cognitive impairment, cardiovascular disease, mental disorders, cancer |
ENG | TWAS, pQTL | No | Carotuximab | Endoglin inhibitor | Age-related macular degeneration, cancer |
CHEK2 | Nearest gene/MAGMA, eQTL coloc | Yes | Prexasertib, XL-844 | Serine/threonine-protein kinase Chk2 inhibitor | Cancer |
ANGPT1 | Nearest gene/MAGMA, eQTL coloc | No | Trebananib, AMG-780 | Angiopoietin-1 inhibitor | Cancer |
PRKCE | Nearest gene/MAGMA, eQTL coloc | No | Midostaurin, KAI-1678 and others | Protein kinase C inhibitor, protein kinase C epsilon inhibitor | Systemic mastocytosis, cancer, pain, psoriasis, liver disease |
COL4A1 | Nearest gene/MAGMA, sQTL coloc | No | Collagenase clostridium histolyticum, ocriplasmin | Collagen hydrolytic enzyme | Macular degeneration and macular holes, diabetic macular edema, retinal vein occlusion |
F2 | MAGMA, pQTL | No | Bivalirudin, argatroban and others | Thrombin inhibitor | Cardiovascular diseases |
COL5A2 | MAGMA, eQTL coloc | No | Collagenase clostridium histolyticum | Collagen hydrolytic enzyme | Macular degeneration and macular holes, diabetic macular edema, retinal vein occlusion, abnormality of connective tissue, stroke |
ITGB5 | MAGMA, eQTL coloc | No | Cilengitide | Integrin alpha-V/beta-5 antagonist | Cancer, kidney disease, myelodysplastic syndrome |
PSMC3 | MAGMA, eQTL coloc | No | Oprozomib | 26S proteosome inhibitor | Cancer |
CRHR1 | MAGMA, eQTL coloc | No | SSR125543, verucerfont and others | Corticotropin releasing factor receptor 1 antagonist | Social anxiety disorder, irritable bowel syndrome, major depressive disorder, congenital adrenal hyperplasia |
MAPT | MAGMA, eQTL/sQTL coloc | No | Gosuranemab, semorinemab and others | Microtubule-associated protein tau inhibitor | Alzheimer’s disease, progressive supranuclear palsy |
NR1H3 | MAGMA, eQTL/sQTL coloc | No | BMS-852927, hyodeoxycholic acid, RGX-104 | LXR-alpha modulator, LXR-alpha agonist, liver X receptor agonist | Hypercholesterolemia, neoplasm |
TGFB3 | MAGMA, sQTL coloc | No | Luspatercept, bintrafusp alfa, fresolimumab | Transforming growth factor beta inhibitor | Myeloproliferative disorder, myelodysplastic syndrome, myelofibrosis, anemia, cancer |
ITGB3 | Nearest gene, sQTL coloc | No | Abciximab, tirofiban and others | Integrin alpha-Iib/beta-3 inhibitor, integrin alpha-V/beta-3 antagonist | Cardiovascular diseases, psoriasis, cancer, COVID-19, anemia |
HTR1F | eQTL coloc | Yes | Almotriptan malate, dexfenfluramine, amisulpride and others | Serotonin 1f (5-HT1f) receptor agonist, serotonin (5-HT) receptor agonist, serotonin (5-HT) receptor antagonist | Mental disorders, dementia, migraine disorder, kidney disease |
PDE6C | eQTL coloc | Yes | Dipyridamole, pentoxifylline | 3′,5′-cyclic phosphodiesterase inhibitor | Duchenne muscular dystrophy, diabetes, diseases of heart, kidney, and liver, cancer, anemia, mental disorders |
RPE65 | Nearest gene | Yes | Emixustat, voretigene neparvovec | Retinoid isomerohydrolase inhibitor, retinoid isomerohydrolase positive modulator | Macular degeneration, diabetic retinopathy, Stargardt disease, retinal dystrophy, Leber congenital amaurosis |
CDC7 | Nearest gene | Yes | BMS-863233, NMS-1116354 | Cell division cycle 7-related protein kinase inhibitor | Refractory hematologic cancer, neoplasm |
TNFSF13B | Nearest gene | Yes | Belimumab, blisibimod and others | Tumor necrosis factor ligand superfamily member 13B inhibitor | Optic neuritis, multiple sclerosis, systemic lupus erythematosus and other immune-related diseases |
CD248 | TWAS | Yes | Ontuxizumab | Endosialin inhibitor | Soft tissue sarcoma, metastatic melanoma, neoplasm |
GSR | TWAS | Yes | Carmustine, oxiglutatione | Glutathione reductase inhibitor, glutathione reductase | Neuromyelitis optica, abnormality of blood tissues, cancer, myelodysplastic syndrome |
LAMB2 | TWAS | Yes | Ocriplasmin | Laminin hydrolytic enzyme | Macular degeneration, macular holes, diabetic macular edema, retinal vein occlusion, uveitis, stroke, deep vein thrombosis |
