Mendelian randomization analysis: investigating the causal association between apoptotic proteins and diabetes

Diabetes, commonly coexisting with hypertension, notably elevates the risk of damage to target organs. Apoptosis, a critical cellular process, maintains physiological balance but its role in the etiology of diabetes remains elusive.

Mendelian randomization analysis.

Utilizing summary data from genome-wide association studies (GWAS) of apoptotic proteins and diabetes, a two-sample Mendelian randomization (MR) design was employed. Our analysis included the Inverse Variance Weighted (IVW), weighted median, weighted mode, and MR-Egger regression. Sensitivity analyses included MR-Egger, MR-PRESSO, Cochran's Q test, and leave-one-out analyses, aimed at assessing and confirming the robustness and reliability of the research findings.

Our analysis revealed a suggestive positive correlation between increased Caspase-10 levels and heightened risk of type 1 diabetes (T1D) (OR 1.15, 95% CI 1.02-1.29, P = 0.02). Similarly, higher serum BCL2 protein levels were found to be nominally associated with an increased risk of developing type 2 diabetes (T2D) (OR 1.21, 95% CI 1.07-1.37, P = 0.003). Conversely, the BCL2L1 protein may exert a suggestive protective effect against T2D (OR 0.92, 95% CI 0.86-0.99, P = 0.03). Sensitivity analyses confirmed the reliability of these findings.

Our study illuminates the genetic causal ties between apoptotic proteins and the susceptibility to essential hypertension and diabetes. These insights are foundational for advancing our comprehension of disease mechanisms, facilitating preventive measures, and opening new horizons for precision medicine targeting these pathways.

The online version contains supplementary material available at 10.1007/s40200-025-01771-w.