Abstract
BACKGROUND: Preterm birth has been associated with an increased risk of myopia, but the causal relationship between these two factors remains unclear. Traditional epidemiological studies are limited by confounding factors and reverse causality. Mendelian randomization (MR) analysis, utilizing genetic variants as instrumental variables, provides a robust approach to investigate causal relationships. In this study, we aimed to explore the potential causal link between preterm birth and myopia risk using a two-sample MR analysis strategy. METHODS: We conducted a Mendelian randomization study to investigate the causal relationship between preterm birth and myopia risk. Genetic variants (single nucleotide polymorphisms, SNPs) were used as instrumental variables, and summary data from genome-wide association studies (GWAS) were utilized. Four regression models, including MR-Egger regression, weighted median regression, inverse variance weighted regression, and Weighted mode regression, were employed to validate the causal relationship. Sensitivity analysis was performed using the leave-one-out method. At the same time, the funnel diagram and MR-Egger test were used to judge the stability of the research results. RESULTS: The MR analysis revealed a significant causal effect of preterm birth on myopia risk. Both the inverse variance weighted regression and weighted median regression models showed a p-value less than 0.05, indicating a robust association. The risk of myopia increased by approximately 30% for everyone standard deviation increase in preterm birth. Sensitivity analysis, funnel plot and MR-Egger test all confirm the stability of the research results. CONCLUSION: Our findings provide evidence supporting a causal relationship between preterm birth and myopia risk. Preterm infants are at a higher risk of developing myopia, and this association is not likely to be influenced by confounding factors or reverse causality. The SNP loci rs6699397, rs10871582, and rs2570497 should be closely monitored as they may lead to abnormal concentrations of intraocular cytokines, particularly vascular endothelial growth factor, potentially elucidating one of the pathogenic mechanisms contributing to the higher incidence of myopia in preterm infants. However the complex interconnections involved extend beyond these factors alone.