Causal association between circulating leukocyte characteristics and diabetic retinopathy based on two-sample...

Area of Science:

• Genetics
• Ophthalmology
• Immunology

Background:

• Leukocytes play a role in diabetic retinopathy (DR) inflammation.
• The exact causal link between leukocyte subtypes and DR risk is unclear.

Purpose of the Study:

• To investigate the causal effect of circulating leukocyte counts on diabetic retinopathy risk using Mendelian randomization.
• To clarify the role of specific leukocyte subtypes in DR pathogenesis.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis.
• Utilized genome-wide association study (GWAS) summary statistics for five leukocyte subtypes and DR in European populations.
• Employed inverse-variance weighted (IVW) method with MR-Egger, weighted median, and MR-PRESSO sensitivity analyses.

Main Results:

• Increased lymphocyte counts showed a significant association with reduced DR risk (OR=0.93, P=0.03).
• An initial association between higher eosinophil counts and increased DR risk was attenuated after outlier correction.
• No significant causal associations were found for basophil, monocyte, or neutrophil counts.

Conclusions:

• Genetic evidence suggests a potential protective role for lymphocytes in diabetic retinopathy.
• The association between eosinophils and DR risk requires further investigation due to attenuation.
• Understanding lymphocyte involvement in DR is crucial for developing targeted prevention and treatment strategies.