Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Endocrinol (Lausanne). 2023 Jan 17;13:1087965. doi: 10.3389/fendo.2022.1087965. eCollection 2022.
This study aimed to investigate the causal association between unhealthy lifestyle factors and diabetic retinopathy (DR) risk and to determine better interventions targeting these modifiable unhealthy factors.
Two-sample Mendelian randomization (MR) analysis was performed in this study. The inverse variance-weighted method was used as the primary method.
Our study included 687 single-nucleotide polymorphisms associated with unhealthy lifestyle factors as instrumental variables. Aggregated data on individual-level genetic information were obtained from the corresponding studies and consortia. A total of 292,622,3 cases and 739,241,18 variants from four large consortia (MRC Integrative Epidemiology Unit [MRC-IEU], Genetic Investigation of Anthropometric Traits [GIANT], GWAS & Sequencing Consortium of Alcohol and Nicotine Use [GSCAN], and Neale Lab) were included.
In the MR analysis, a higher body mass index (BMI) (odds ratio [OR], 95% confidence interval [CI] = 1.42, 1.30-1.54; < 0.001] and cigarettes per day (OR, 95% CI = 1.16, 1.05-1.28; = 0.003) were genetically predicted to be causally associated with an increased risk of DR, while patients with higher hip circumference (HC) had a lower risk of DR (OR, 95% CI = 0.85, 0.76-0.95; = 0.004). In the analysis of subtypes of DR, the results of BMI and HC were similar to those of DR, whereas cigarettes per day were only related to proliferative DR (PDR) (OR, 95% CI = 1.18, 1.04-1.33; = 0.009). In the MR-PRESSO analysis, a higher waist-to-hip ratio (WHR) was a risk factor for DR and PDR (OR, 95% CI = 1.24, 1.02-1.50, = 0.041; OR, 95% CI = 1.32, 1.01-1.73, = 0.049) after removing the outliers. Furthermore, no pleiotropy was observed in these exposures.
Our findings suggest that higher BMI, WHR, and smoking are likely to be causal factors in the development of DR, whereas genetically higher HC is associated with a lower risk of DR, providing insights into a better understanding of the etiology and prevention of DR.
本研究旨在探讨不健康生活方式因素与糖尿病视网膜病变（DR）风险之间的因果关联，并确定针对这些可改变的不健康因素的更好干预措施。
本研究进行了两样本孟德尔随机化（MR）分析。使用逆方差加权法作为主要方法。
我们的研究纳入了 687 个与不健康生活方式因素相关的单核苷酸多态性作为工具变量。个体水平遗传信息的汇总数据来自相应的研究和联盟。共纳入了来自四个大型联盟（MRC 综合流行病学单位 [MRC-IEU]、遗传研究所测特征 [GIANT]、GWAS 和酒精与尼古丁使用测序联盟 [GSCAN]和 Neale 实验室）的 2926223 例个体和 73924118 个变异体。
在 MR 分析中，较高的体重指数（BMI）（比值比 [OR]，95%置信区间 [CI] = 1.42，1.30-1.54；<0.001）和每天吸烟量（OR，95%CI = 1.16，1.05-1.28； = 0.003）被遗传预测为与 DR 风险增加有关，而较高的臀围（HC）与较低的 DR 风险相关（OR，95%CI = 0.85，0.76-0.95； = 0.004）。在 DR 亚型的分析中，BMI 和 HC 的结果与 DR 的结果相似，而每天吸烟量仅与增殖性 DR（PDR）有关（OR，95%CI = 1.18，1.04-1.33； = 0.009）。在 MR-PRESSO 分析中，较高的腰臀比（WHR）是 DR 和 PDR 的危险因素（OR，95%CI = 1.24，1.02-1.50， = 0.041；OR，95%CI = 1.32，1.01-1.73， = 0.049），在剔除离群值后。此外，在这些暴露中没有观察到 pleiotropy。
我们的研究结果表明，较高的 BMI、WHR 和吸烟可能是 DR 发生的因果因素，而遗传上较高的 HC 与 DR 风险降低相关，这为更好地了解 DR 的病因和预防提供了新的视角。
