Abstract
PURPOSE: The role of plasma metabolites in myopia is still unclear, and previous studies are limited by various factors and were mostly observational. This study aims to investigate the causal relationship between plasma metabolites and myopia using 2-sample Mendelian randomization (MR). DESIGN: A 2-sample MR study. SUBJECTS AND PARTICIPANTS: This study analyzed plasma metabolites consisting of 1091 metabolites and 309 metabolite ratios in 8299 individuals from the Canadian Longitudinal Study on Aging cohort. Summary statistics for myopia were obtained from the UK Biobank, encompassing 37 362 cases and 460 536 controls. METHODS: Causal effect estimates were primarily derived using the inverse variance weighting (IVW) method and the constrained maximum likelihood and model averaging-based MR method. Statistical significance for the MR effect estimate was defined as a false discovery rate (FDR) of <0.05. Additionally, we used the MR Steiger directionality test to examine whether exposure was directionally causal for the outcome. Furthermore, 4 supplementary methods were used for analysis: weighted median, MR-Egger, simple mode, and weighted mode. MAIN OUTCOME MEASURES: Genetic causal association between plasma metabolites and myopia. RESULTS: The IVW analysis results indicated that elevated levels of 1-arachidonoyl-GPE (20:4n6) (P_FDR = 5.80E-06), linoleoyl-arachidonoyl glycerol (18:2/20:4)[1] (P_FDR = 2.24E-06), and linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2](P_FDR = 0.0242) have a protective effect on myopia. Elevated levels of 4 plasma metabolite ratios, including the phosphate to linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2] ratio (P_FDR = 0.0029), citrulline to dimethylarginine (SDMA + ADMA) ratio (P_FDR = 0.0207), oleoyl-linoleoyl-glycerol (18:1/18:2) [2] to linoleoyl-arachidonoyl-glycerol (18:2/20:4) [1] ratio (P_FDR = 0.0230), and retinol (vitamin A) to linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2] ratio (P_FDR = 0.0230), were significantly associated with a higher risk of myopia. CONCLUSIONS: This study provides evidence of a causal relationship between specific plasma metabolites and myopia, highlighting potential therapeutic targets and contributing to the understanding of myopia's etiology. Future research should include diverse populations to enhance the generalizability of these findings. FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.