Potential disease biomarkers for diabetic retinopathy identified through Mendelian randomization analysis

Xuyan Zou; Suna Ye; Yao Tan

doi:10.3389/fendo.2023.1339374

Potential disease biomarkers for diabetic retinopathy identified through Mendelian randomization analysis

Front Endocrinol (Lausanne). 2024 Jan 11:14:1339374. doi: 10.3389/fendo.2023.1339374. eCollection 2023.

Authors

Xuyan Zou^#¹, Suna Ye^#², Yao Tan^{3

4}

Affiliations

¹ Changsha Aier Eye Hospital, Aier Eye Hospital Group, Changsha, China.
² Senzhen Aier Eye Hospital, Jinan University, Shenzhen, China.
³ Department of Ophthalmology, The Third Xiangya Hospital, Central South University, Changsha, China.
⁴ Postdoctoral Station of Clinical Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.

^# Contributed equally.

Abstract

Background: Diabetic retinopathy (DR), a leading cause of vision loss, has limited options for effective prevention and treatment. This study aims to utilize genomics and proteomics data to identify potential drug targets for DR.

Methods: We utilized plasma protein quantitative trait loci data from the Atherosclerosis Risk in Communities Study and the Icelandic Decoding Genetics Study for discovery and replication, respectively. Genetic associations with DR, including its subtypes, were derived from the FinnGen study. Mendelian Randomization (MR) analysis estimated associations between protein levels and DR risk, complemented by colocalization analysis to examine shared causal variants.

Results: Our MR analysis identified significant associations of specific plasma proteins with DR and proliferative DR (PDR). Elevated genetically predicted levels of WARS (OR = 1.16; 95% CI = 0.095-0.208, FDR = 1.31×10^-4) and SIRPG (OR = 1.15; 95% CI = 0.071-0.201, FDR = 1.46×10^-2) were associated with higher DR risk, while increased levels of ALDOC (OR = 1.56; 95% CI = 0.246-0.637, FDR = 5.48×10^-3) and SIRPG (OR = 1.15; 95% CI = 0.068-0.208, FDR = 4.73×10^-2) were associated with higher PDR risk. These findings were corroborated by strong colocalization evidence.

Conclusions: Our study highlights WARS, SIRPG, and ALDOC as significant proteins associated with DR and PDR, providing a basis for further exploration in drug development. Additional studies are needed to validate these proteins as disease biomarkers across diverse populations.

Keywords: Mendelian randomization; diabetic retinopathy; disease biomarkers; genomics; proteomics.

Publication types

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

MeSH terms

Biomarkers
Blood Proteins
Diabetes Mellitus*
Diabetic Retinopathy* / diagnosis
Diabetic Retinopathy* / genetics
Humans
Mendelian Randomization Analysis

Substances

Blood Proteins
Biomarkers

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Funded Postdoctoral Researcher Program of China (GZC20233180).