Lu Yi, Zhang Can-Can, Ma Run-Ting, Li Yuan-Jing, Li Wen-Ping, Hu Die-Wen-Jie, Zhou Lian-Hong
Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Int J Ophthalmol. 2024 Nov 18;17(11):2082-2092. doi: 10.18240/ijo.2024.11.15. eCollection 2024.
To study the causal relationship between obesity-related anthropometric traits and myopia and the mediating role of educational attainment (EA).
Univariable Mendelian randomization (UVMR) was performed to evaluate the causal association between body mass index (BMI), height, waist-hip ratio (WHR, adjusted for BMI), and mean spherical equivalent (MSE). BMI was divided into fat and fat-free mass and included in multivariable Mendelian randomization (MVMR) to explore the roles of different BMI components in the causal relationship between BMI and MSE. A mediation analysis based on two-step Mendelian randomization (MR) was carried out. Specifically, UVMR was conducted to estimate the causal effect of BMI on EA. The direct effect of EA on MSE was estimated from MVMR. The mediation effect of EA in the BMI-EA-MSE model was calculated by the product of coefficients method. Expression quantitative trait loci (eQTL)-MR, reverse MR, and Linkage Disequilibrium Score Regression (LDSC) were performed to assess the robustness.
Genetically predicted higher BMI had a positive total effect on MSE (IVW=0.26 D, 95%CI=0.14 to 0.37 D, <0.001), whereas there was no significant association between height, WHR, and MSE. Fat mass was found to play a significant role in the effect of body mass on MSE (IVW=0.50 D, 95%CI=0.21 to 0.78 D, =0.001), but there was no significant association between fat-free mass and MSE. The causal effect of BMI on EA was -0.14 (95%CI=-0.16 to -0.11, <0.001), and the direct effect of EA on MSE was -0.63 D (95%CI=-0.81 to -0.44 D, <0.001). The mediating effect of EA in the BMI-EA-MSE model was 0.09 D (95%CI=0.06 to 0.12 D), with a mediation proportion of 33% (95%CI=22.1% to 44.6%). No reverse causal associations were detected except for BMI on EA. The results of eQTL-MR and LDSC were consistent with each MR analysis.
Genetically predicted higher BMI decreases the degree of myopia with a 33% mediation proportion by EA, and fat mass provides a dominant protective role in body mass-myopia. As a supplement to previous observational studies, it provides strong evidence for the relationship between anthropometric traits and refractive errors and offers a theoretical basis for future measures to prevent and control myopia.
研究肥胖相关人体测量学特征与近视之间的因果关系以及教育程度（EA）的中介作用。
进行单变量孟德尔随机化（UVMR）以评估体重指数（BMI）、身高、腰臀比（调整BMI后的WHR）与平均球镜当量（MSE）之间的因果关联。将BMI分为脂肪量和去脂体重，并纳入多变量孟德尔随机化（MVMR）以探讨不同BMI成分在BMI与MSE因果关系中的作用。基于两步孟德尔随机化（MR）进行中介分析。具体而言，进行UVMR以估计BMI对EA的因果效应。从MVMR估计EA对MSE的直接效应。通过系数乘积法计算EA在BMI-EA-MSE模型中的中介效应。进行表达数量性状位点（eQTL）-MR、反向MR和连锁不平衡评分回归（LDSC）以评估稳健性。
遗传预测的较高BMI对MSE有正向总效应（IVW = 0.26 D，95%CI = 0.14至0.37 D，<0.001），而身高、WHR与MSE之间无显著关联。发现脂肪量在体重对MSE的影响中起显著作用（IVW = 0.50 D，95%CI = 0.21至0.78 D，= 0.001），但去脂体重与MSE之间无显著关联。BMI对EA的因果效应为-0.14（95%CI = -0.16至-0.11，<0.001），EA对MSE的直接效应为-0.63 D（95%CI = -0.81至-0.44 D，<0.001）。EA在BMI-EA-MSE模型中的中介效应为0.09 D（95%CI = 0.06至0.12 D），中介比例为33%（95%CI = 22.1%至44.6%）。除BMI对EA外，未检测到反向因果关联。eQTL-MR和LDSC的结果与每项MR分析一致。
遗传预测的较高BMI可降低近视程度，其中EA的中介比例为33%，且脂肪量在体重-近视关系中起主要保护作用。作为对先前观察性研究的补充，它为人体测量学特征与屈光不正之间的关系提供了有力证据，并为未来预防和控制近视的措施提供了理论基础。
