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Causal associations of antihypertensive and lipid-lowering drugs with ocular diseases: a cross-ancestry drug target Mendelian randomization study
- CHEN Changhai, ZHANG Xiumei, YUAN Zhongshang, WANG Shukang
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Journal of Shandong University (Health Sciences). 2026, 64(7):
69-80.
doi:10.6040/j.issn.1671-7554.0.2025.1059
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Objective To investigate the causal associations between commonly used antihypertensive and lipid-lowering drugs and prevalent ocular diseases in East Asian and European populations using drug-target Mendelian randomization(MR). Methods This cross-ancestry drug-target MR study utilized publicly available genome-wide association study(GWAS)summary data from the GWAS Catalog. Five classes of antihypertensive drugs, including angiotensin-converting enzyme inhibitors(ACEIs), angiotensin II receptor blockers(ARBs), β-blockers(BBs), calcium channel blockers(CCBs), and thiazide diuretics(TDs), and three classes of lipid-lowering drugs, including 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)inhibitors, proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors, and Niemann–Pick C1-like 1(NPC1L1)inhibitors were selected as exposures. Six common ocular diseases(senile cataract, glaucoma, dry eye syndrome, visual impairment, presbyopia, and myopia)were defined as outcomes. Inverse variance weighted(IVW)was employed as the primary analytical method, supplemented by seven additional MR methods for findings with statiscauy significant correlation. Sensitivity analyses were conducted using Cochrans Q test, MR-Egger intercept test, and leave-one-out analysis. Results In East Asian populations, ACEIs were causally associated with increased risks of myopia(OR=1.024, 95%CI: 1.010-1.038, PFDR=0.002), senile cataract(OR=1.022, 95%CI: 1.019-1.024, PFDR<0.001), and glaucoma(OR=1.017, 95%CI: 1.011-1.023, PFDR<0.001); BBs were associated with reduced risk of senile cataract(OR=0.994, 95%CI: 0.989-0.999, PFDR=0.034); PCSK9 inhibitors were associated with reduced risks of presbyopia(OR=0.993, 95%CI: 0.986-0.997, PFDR=0.003)and visual impairment(OR=0.996, 95%CI: 0.992-0.999, PFDR=0.048). In European populations, ACEIs were associated with increased glaucoma risk(OR=1.088, 95%CI: 1.029-1.152, PFDR=0.016); HMGCR inhibitors were associated with increased senile cataract risk(OR=1.194, 95%CI: 1.049-1.359, PFDR=0.022); PCSK9 inhibitors were associated with increased risks of dry eye syndrome(OR=1.106, 95%CI: 1.039-1.176, PFDR=0.004)and presbyopia(OR=1.082, 95%CI: 1.024-1.145, PFDR=0.017), but with reduced glaucoma risk(OR=0.892, 95%CI: 0.822-0.968, PFDR=0.018); NPC1L1 inhibitors were associated with reduced glaucoma risk(OR=0.706, 95%CI: 0.579-0.861, PFDR=0.002). Conclusion ACEIs may increase risks of certain ocular diseases in both East Asian and European populations. BBs may reduce senile cataract risk in East Asians. HMGCR inhibitors may increase cataract risk in Europeans, while NPC1L1 inhibitors may reduce glaucoma risk in Europeans. The effects of PCSK9 inhibitors on ocular diseases exhibit ethnic differences.
