Association between Plasma Metabolite Levels and Myopia: A 2-Sample Mendelian Randomization Study

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2024-12-30 DOI:10.1016/j.xops.2024.100699

Xiaohui Jiang MD , Boyue Xu MD , Qiyuan Li MD , Yun-e Zhao MD

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引用次数: 0

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 Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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血浆代谢物水平与近视之间的关系：一项两样本孟德尔随机研究

目的血浆代谢物在近视中的作用尚不清楚，以往的研究受各种因素的限制，多为观察性研究。本研究旨在通过两样本孟德尔随机化（MR）研究血浆代谢物与近视之间的因果关系。设计2个样本的MR研究。受试者和参与者本研究分析了来自加拿大老龄化纵向研究队列的8299名个体的血浆代谢物，包括1091种代谢物和309种代谢物比率。近视的汇总统计数据来自英国生物银行，包括37362例和460 536例对照。方法主要使用逆方差加权（IVW）方法、约束最大似然和基于模型平均的MR方法得出因果效应估计。MR效应估计的统计显著性定义为错误发现率（FDR）为0.05。此外，我们使用MR Steiger方向性检验来检验暴露是否对结果有方向性因果关系。此外，采用加权中位数、MR-Egger、简单模型和加权模型4种辅助方法进行分析。血浆代谢物与近视之间的遗传因果关系。结果IVW分析结果显示，1-花生四烯酰基gpe (20:4n6) （P_FDR = 5.80E-06）、亚油基花生四烯酰基甘油（18:2/20:4）[1]（P_FDR = 2.24E-06）和亚油基花生四烯酰基甘油（18:2/20:4）[2]（P_FDR = 0.0242）水平升高对近视具有保护作用。血浆代谢物中磷酸与亚油基花生四烯酰基甘油（18:2/20:4）[2]比值（P_FDR = 0.0029）、瓜氨酸与二甲基精氨酸（SDMA + ADMA）比值（P_FDR = 0.0207）、油基-亚油基甘油（18:1/18:2）[2]与亚油基花生四烯酰基甘油（18:2/20:4）[1]比值（P_FDR = 0.0230）、视黄醇（维生素A）与亚油基花生四烯酰基甘油（18:2/20:4）[2]比值（P_FDR = 0.0230）升高与近视风险显著相关。结论本研究为特定血浆代谢物与近视之间的因果关系提供了证据，突出了潜在的治疗靶点，有助于了解近视的病因。未来的研究应包括不同的人群，以提高这些发现的普遍性。财务披露作者在本文中讨论的任何材料中没有专有或商业利益。

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