Diabetic retinopathy risk in patients with unhealthy lifestyle: A Mendelian randomization study

Zixuan Su; Zhixin Wu; Xueqing Liang; Meng Xie; Jia Xie; Huiqing Li; Xinghua Wang; Fagang Jiang

doi:10.3389/fendo.2022.1087965

Diabetic retinopathy risk in patients with unhealthy lifestyle: A Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Jan 17:13:1087965. doi: 10.3389/fendo.2022.1087965. eCollection 2022.

Authors

Zixuan Su¹, Zhixin Wu², Xueqing Liang³, Meng Xie¹, Jia Xie¹, Huiqing Li², Xinghua Wang¹, Fagang Jiang¹

Affiliations

¹ Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, China.

Abstract

Purpose: 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.

Design: Two-sample Mendelian randomization (MR) analysis was performed in this study. The inverse variance-weighted method was used as the primary method.

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.

Result: In the MR analysis, a higher body mass index (BMI) (odds ratio [OR], 95% confidence interval [CI] = 1.42, 1.30-1.54; P < 0.001] and cigarettes per day (OR, 95% CI = 1.16, 1.05-1.28; P = 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; P = 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; P = 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, P = 0.041; OR, 95% CI = 1.32, 1.01-1.73, P = 0.049) after removing the outliers. Furthermore, no pleiotropy was observed in these exposures.

Conclusion: 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.

Keywords: Mendelian randomization; alcohol intake; diabetic retinopathy; obesity; smoking; unhealthy lifestyle factors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Body Mass Index
Diabetes Mellitus*
Diabetic Retinopathy* / etiology
Diabetic Retinopathy* / genetics
Humans
Mendelian Randomization Analysis
Risk Factors
Waist-Hip Ratio

Grants and funding

This work was supported by the National Natural Science Foundation of China (No.81900912). The funding organization had no role in the design or conduct of this study.