Genetic correlation between circulating cytokines and risk of three ophthalmic diseases: a bidirectional two-sample Mendelian randomization study

Xin Zhang; Qiangqiang Fu; Yuying Cai; Xianglian Li; Li Chen; Yaping Jiang; Yihui Chen

doi:10.1093/hmg/ddae041

Genetic correlation between circulating cytokines and risk of three ophthalmic diseases: a bidirectional two-sample Mendelian randomization study

Hum Mol Genet. 2024 Apr 23:ddae041. doi: 10.1093/hmg/ddae041. Online ahead of print.

Authors

Xin Zhang¹, Qiangqiang Fu², Yuying Cai¹, Xianglian Li¹, Li Chen¹, Yaping Jiang¹, Yihui Chen¹

Affiliations

¹ Department of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, 450 Tengyue Road, Shanghai 200090, China.
² Department of General Practice, Clinical Research Center for General Practice, Yangpu Hospital, School of Medicine, Tongji University, 450 Tengyue Road, Shanghai 200090, China.

PMID: 38664229
DOI: 10.1093/hmg/ddae041

Abstract

Purpose: Pathogenesis and the associated risk factors of cataracts, glaucoma, and age-related macular degeneration (AMD) remain unclear. We aimed to investigate causal relationships between circulating cytokine levels and the development of these diseases.

Patients and methods: Genetic instrumental variables for circulating cytokines were derived from a genome-wide association study of 8293 European participants. Summary-level data for AMD, glaucoma, and senile cataract were obtained from the FinnGen database. The inverse variance weighted (IVW) was the main Mendelian randomization (MR) analysis method. The Cochran's Q, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used for sensitivity analysis.

Results: Based on the IVW method, MR analysis demonstrated five circulating cytokines suggestively associated with AMD (SCGF-β, 1.099 [95%CI, 1.037-1.166], P = 0.002; SCF, 1.155 [95%CI, 1.015-1.315], P = 0.029; MCP-1, 1.103 [95%CI, 1.012-1.202], P = 0.026; IL-10, 1.102 [95%CI, 1.012-1.200], P = 0.025; eotaxin, 1.086 [95%CI, 1.002-1.176], P = 0.044), five suggestively linked with glaucoma (MCP-1, 0.945 [95%CI, 0.894-0.999], P = 0.047; IL1ra, 0.886 [95%CI, 0.809-0.969], P = 0.008; IL-1β, 0.866 [95%CI, 0.762-0.983], P = 0.027; IL-9, 0.908 [95%CI, 0.841-0.980], P = 0.014; IL2ra, 1.065 [95%CI, 1.004-1.130], P = 0.035), and four suggestively associated with senile cataract (TRAIL, 1.043 [95%CI, 1.009-1.077], P = 0.011; IL-16, 1.032 [95%CI, 1.001-1.064], P = 0.046; IL1ra, 0.942 [95%CI, 0.887-0.999], P = 0.047; FGF-basic, 1.144 [95%CI, 1.052-1.244], P = 0.002). Furthermore, sensitivity analysis results supported the above associations.

Conclusion: This study highlights the involvement of several circulating cytokines in the development ophthalmic diseases and holds potential as viable pharmacological targets for these diseases.

Keywords: Mendelian randomization; causality; circulating cytokines; ophthalmic diseases.

Grants and funding

82271050/National Natural Science Foundation of China