BMI and plasma lipid levels with risk of proliferative diabetic retinopathy: a univariable and multivariable Mendelian randomization study

Yiyang Shu; Qi Zhou; Yuting Shao; Hui Lin; Shen Qu; Wenting Han; Xiao Lv; Yanlong Bi

doi:10.3389/fnut.2023.1099807

BMI and plasma lipid levels with risk of proliferative diabetic retinopathy: a univariable and multivariable Mendelian randomization study

Front Nutr. 2023 Sep 13:10:1099807. doi: 10.3389/fnut.2023.1099807. eCollection 2023.

Authors

Yiyang Shu¹, Qi Zhou², Yuting Shao¹, Hui Lin¹, Shen Qu¹, Wenting Han¹, Xiao Lv¹, Yanlong Bi^{1

3}

Affiliations

¹ Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
² Exam Center, School of Medicine, Tongji University, Shanghai, China.
³ School of Medicine, Tongji Eye Institute, Tongji University, Shanghai, China.

Abstract

Background: The study aimed to determine whether a causal effect exists between body mass index (BMI) or plasma lipid levels and proliferative diabetic retinopathy (PDR) risk in humans.

Methods: We utilized univariable (UVMR) and multivariable two-sample Mendelian randomization (MVMR) analyses to confirm the effects of BMI and plasma lipid levels on the risk of PDR. Genetic variants associated with BMI and three plasma lipids were obtained from GWAS summary datasets generated by many different consortia and were deposited in the MR-Base database. The GWAS summary data for PDR from the FinnGen biobank included 2,12,889 participants of European ancestry (8,681 cases and 2,04,208 controls). Inverse variance weighted (IVW) was applied as the main MR analysis. Sensitivity analysis was used to evaluate the robustness of our findings.

Results: In the UVMR analysis, the causal associations of genetically predicted BMI with PDR presented a positive association (OR = 1.120, 95% CI = 1.076-1.167, P < 0.001), and the lower HDL-C level was associated with a higher risk of PDR (OR = 0.898, 95% CI = 0.811-0.995, P = 0.040). No evidence of an association between LDL-C or TG levels (P > 0.05) and PDR risk was found. In the MVMR analysis controlling for the HDL-C level, there was strong evidence for a direct causal effect of BMI on the risk of PDR (OR = 1.106, 95%CI = 1.049, 1.166, P < 0.001, IVW). After adjusting for BMI, there was no evidence for a direct causal effect of the HDL-C level on the risk of PDR (OR = 0.911, 95% CI = 0.823, 1.008, P = 0.072). Sensitivity analyses confirmed that the results were reliable and stable.

Conclusion: Robust evidence was demonstrated for an independent, causal effect of BMI in increasing the risk of PDR. Further studies are required to understand the potential biological mechanisms underlying this causal relationship.

Keywords: Mendelian randomization; body mass index (BMI); causal effect; dyslipidemia; proliferative diabetic retinopathy (PDR).

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (Grant No. 82070920), project supported by the Clinical Research Project of Tongji Hospital of Tongji University [ITJ(ZD)2101], and the Excellent Personnel Training Plan for the Shanghai Health System (SHDC2022CRD008). The sponsor or funding organization had no role in the design or conduct of this research.