Causal relationships between 41 inflammatory cytokines and myopia: a Mendelian randomization study

To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization (MR) approach.

Publicly available genome-wide association study (GWAS) datasets were utilized for this two-sample MR analysis. Inflammatory cytokine-related GWAS data were extracted from The University of Bristol’s Research Data Repository, and myopia-related GWAS data were obtained from the FinnGen project. Single nucleotide polymorphisms (SNPs) associated with inflammatory cytokines were systematically selected as instrumental variables (IVs) based on three rigorous criteria: relevance, independence, and exclusion of pleiotropy. Five MR methods were employed for causal inference: the inverse-variance weighted (IVW) method as the primary analysis, supplemented by MR-Egger regression, weighted median estimator, simple mode, and weighted mode approaches. Sensitivity analyses were performed to evaluate the robustness of the causal estimates.

A total of 773 myopia-associated SNPs were identified. MR analysis revealed that higher levels of macrophage inflammatory protein 1-α (MIP-1α) were associated with a 17% reduced risk of myopia [odds ratio (OR)=0.83; 95% confidence interval (CI): 0.69-0.99; P<0.05]. In contrast, elevated levels of eotaxin (OR=1.26; 95%CI: 1.07-1.47; P<0.01), stromal cell-derived factor-1α (SDF-1α; OR=1.68; 95% CI: 1.08-2.62; P<0.05), and interleukin-2 receptor subunit alpha (IL-2Rα; OR=1.25; 95%CI: 1.01-1.53; P<0.05) were significantly associated with an increased risk of myopia. Sensitivity analyses confirmed the reliability of these results.

This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia. MIP-1α may act as a protective factor against myopia, while eotaxin, SDF-1α, and IL-2Rα are potential risk factors for myopia. These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia, offering novel insights for the development of preventive and therapeutic strategies for myopia.