Genetic prediction of the relationship between mitochondrial proteins and diabetic polyneuropathy risk: a Mendelian randomization study

This Mendelian Randomization (MR) study investigates the causal relationships between mitochondrial proteins and Diabetic polyneuropathy (DPN). Using a two-sample MR design with data from FINNGEN (1048 DPN cases, 374,434 controls) and 63 mitochondrial proteins from GWAS datasets. Analyses used the Inverse Variance Weighted (IVW) method, MR-Egger regression, and weighted medians, with extensive sensitivity tests for robustness. Elevated COA3 levels (OR = 0.5774, 95% CI: 0.4466-0.7465, p < 0.01) decreased DPN risk, while elevated NFU1 (OR: 1.3992, 95% CI: 1.0935-1.7904, p = 0.0075) and SARS2 (OR: 1.3660, 95% CI: 1.0651-1.7520, p = 0.0140) increased risk. COA3, NFU1, and SARS2 significantly affect DPN risk, with COA3 lowering and NFU1 and SARS2 increasing risk. These findings highlight potential targets for DPN prevention and treatment, suggesting the importance of mitochondrial proteins in DPN pathogenesis, and providing new insights for future therapeutic strategies to effectively combat this debilitating condition.