Purpose: Though the pathogenesis of myopia remains unclear, emerging evidence suggests a potential link between the onset of myopia and systemic inflammation. This study aims to elucidate the causal relationships between the two via Mendelian randomization (MR).
Methods: We utilized genome-wide association study data on circulating inflammatory proteins (n = 14,824), immune cell traits (n = 3757), and myopia (n cases = 4106, n controls = 394,028) for a standard two-sample bidirectional MR analysis, followed by sensitivity analyses employing diverse approaches. The validation of seven inflammatory molecules was conducted through ELISA analysis of 116 plasma samples from a hospital-based cohort, as well as proteomics data from 3310 participants in the UK Biobank cohort.
Results: Our analysis identified three inflammatory proteins (CXCL9, CXCL11, and T cell surface glycoprotein CD5) and six immune phenotypes, primarily related to T cells, as risk factors for myopia, and IL-5 and eight traits as protective factors. Meanwhile, we observed that myopia may elevate the levels of two inflammatory agents (TNFRSF9 and IL-24) and 12 peripheral immunophenotypes, predominantly associated with T cells and monocytes. Validation analysis in two independent cohorts further corroborated the proinflammatory state in highly myopic patients manifested by significantly elevated plasma levels of CXCL9, CXCL11, and TNFRSF9.
Conclusions: Our study identified a potential bidirectional causal relationship between systemic immune dynamics and myopia, underscoring the importance of considering myopia in the context of systemic condition. Research is warranted to further identify underlying mechanisms.
Keywords: Mendelian randomization; Myopia; Systemic inflammation.
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