Causal relationships between blood metabolites and diabetic retinopathy: a two-sample Mendelian randomization study

Chongchao Yang; Yan Ma; Mudi Yao; Qin Jiang; Jinsong Xue

doi:10.3389/fendo.2024.1383035

Causal relationships between blood metabolites and diabetic retinopathy: a two-sample Mendelian randomization study

Front Endocrinol (Lausanne). 2024 May 1:15:1383035. doi: 10.3389/fendo.2024.1383035. eCollection 2024.

Authors

Chongchao Yang^{1

2}, Yan Ma^{1

2}, Mudi Yao³, Qin Jiang^{1

2}, Jinsong Xue^{1

2}

Affiliations

¹ The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
² The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
³ Department of Ophthalmology, The First People's Hospital, Shanghai, China.

Abstract

Background: Diabetic retinopathy (DR) is a microvascular complication of diabetes, severely affecting patients' vision and even leading to blindness. The development of DR is influenced by metabolic disturbance and genetic factors, including gene polymorphisms. The research aimed to uncover the causal relationships between blood metabolites and DR.

Methods: The two-sample mendelian randomization (MR) analysis was employed to estimate the causality of blood metabolites on DR. The genetic variables for exposure were obtained from the genome-wide association study (GWAS) dataset of 486 blood metabolites, while the genetic predictors for outcomes including all-stage DR (All DR), non-proliferative DR (NPDR) and proliferative DR (PDR) were derived from the FinnGen database. The primary analysis employed inverse variance weighted (IVW) method, and supplementary analyses were performed using MR-Egger, weighted median (WM), simple mode and weighted mode methods. Additionally, MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were also conducted to guarantee the accuracy and robustness of the results. Subsequently, we replicated the MR analysis using three additional datasets from the FinnGen database and conducted a meta-analysis to determine blood metabolites associated with DR. Finally, reverse MR analysis and metabolic pathway analysis were performed.

Results: The study identified 13 blood metabolites associated with All DR, 9 blood metabolites associated with NPDR and 12 blood metabolites associated with PDR. In summary, a total of 21 blood metabolites were identified as having potential causal relationships with DR. Additionally, we identified 4 metabolic pathways that are related to DR.

Conclusion: The research revealed a number of blood metabolites and metabolic pathways that are causally associated with DR, which holds significant importance for screening and prevention of DR. However, it is noteworthy that these causal relationships should be validated in larger cohorts and experiments.

Keywords: Mendelian randomization; blood metabolites; diabetic retinopathy; meta-analysis; metabolic pathway analysis.

MeSH terms

Diabetic Retinopathy* / blood
Diabetic Retinopathy* / genetics
Genome-Wide Association Study*
Humans
Mendelian Randomization Analysis*
Polymorphism, Single Nucleotide

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research received financial support from the National Natural Science Foundation of China (grant number no. 82070983).