Exploring causal correlations between immune cells and diabetic neuropathy: a Mendelian randomization

Area of Science:

• Immunology
• Genetics
• Neurology

Background:

• Circulating immune cells are implicated in diabetic neuropathy (DN) development.
• Establishing causal links between biomarkers and diseases like DN is challenging.
• Mendelian Randomization (MR) offers a method to investigate causal relationships using genetic data.

Purpose of the Study:

• To conduct a bidirectional two-sample MR analysis.
• To investigate the causal relationship between immune cell phenotypes and diabetic neuropathy (DN).

Main Methods:

• Utilized genome-wide association study (GWAS) summary statistics.
• Analyzed immune cell phenotypes from 3,757 Sardinian individuals.
• Obtained DN data from the FinnGen database.
• Performed sensitivity analyses, assessed horizontal pleiotropy (MR-Egger, MR-Presso), and evaluated heterogeneity (Cochran's Q test).
• Applied False Discovery Rate correction.

Main Results:

• Identified 24 immune cell phenotypes significantly associated with DN risk.
• Positive correlations with DN risk included CD45 on myeloid cells, HLA DR on monocytes, and CD27 on B cells.
• Negative correlations with DN risk involved specific T cell types, including CD28- T cells and HLA DR+ T cells.

Conclusions:

• Demonstrated the immunological susceptibility of DN.
• Clarified the influence of immune responses on DN progression.
• Findings may guide the development of novel immunological therapies and diagnostic/treatment targets for DN.