Relationship between circulating metabolites and diabetic retinopathy: a two-sample Mendelian randomization analysis
Lingli Ma1, Ying Dong2, Zimeng Li1
1Department of Endocrinology and Metabolism, China-Japan Union Hospital of Jilin University, 126 Sendai Avenue, Changchun City, Jilin Province, China.
Scientific Reports
|February 29, 2024
Summary
This study identifies specific blood metabolites associated with diabetic retinopathy (DR) risk. Certain metabolites may offer protective effects, while others increase susceptibility, aiding in understanding DR mechanisms and drug target selection.
Area of Science:
- Genetics and Metabolomics
- Ophthalmology
- Endocrinology
Background:
- Diabetic retinopathy (DR) is a leading microvascular complication of diabetes mellitus, yet its biological underpinnings are not fully understood.
- Identifying key metabolites involved in DR pathogenesis is crucial for developing targeted interventions and improving patient outcomes.
Purpose of the Study:
- To investigate the causal relationship between genetically predicted circulating metabolite levels and the risk of developing diabetic retinopathy (DR).
- To identify potential metabolite-based biomarkers and therapeutic targets for DR.
Main Methods:
- Genome-wide association studies (GWAS) were performed on individuals of European ancestry to link single nucleotide polymorphisms (SNPs) with 486 blood metabolites.
- Two-sample Mendelian randomization (MR) analysis was employed using the FinnGen Biobank database to assess the association between metabolite levels and DR susceptibility.
- Sensitivity analyses, including weighted median, weighted mode, and MR-Egger, were conducted to ensure the robustness of the findings.
Main Results:
- Several metabolites, including 1-oleoylglycerophosphoethanolamine, pyroglutamine, phenyllactate (PLA), metoprolol acid metabolite, 10-undecenoate, erythritol, 1-stearoylglycerophosphoethanolamine, and 1-arachidonoylglycerophosphoethanolamine, showed a significant protective association with DR.
- Conversely, elevated levels of stachydrine, butyrylcarnitine, 5-oxoproline, and kynurenine were significantly associated with an increased risk of DR.
- The identified metabolites demonstrate potential as prospective compounds for investigating DR mechanisms and selecting drug targets.
Conclusions:
- This study highlights specific circulating metabolites with significant causal links to diabetic retinopathy risk, suggesting their involvement in disease pathogenesis.
- The findings provide a foundation for future research into the biological pathways underlying DR and the development of novel therapeutic strategies.
- Metabolite profiling may offer new avenues for early detection, risk stratification, and personalized treatment of diabetic retinopathy.
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