The causal association between cardiovascular proteins and diabetic nephropathy: a Mendelian randomization study

Abstract

Purpose: To clarify the causal association between cardiovascular proteins and diabetic nephropathy (DN) in Europeans.

Methods: The large genome-wide association study data of cardiovascular proteins and DN were used for this two-sample Mendelian randomization (MR) analysis. We took the Inverse variance weighted (IVW) as the primary method. Moreover, MR-Egger, weighted median, weighted mode, and simple mode were also performed as supplementary methods. Further, Cochrane's Q test, MR-Egger, and MR-PRESSO were conducted for sensitivity analysis.

Results: According to the IVW method, the results indicated that Galanin peptide was a protective factor for DN (OR: 0.835, 95% CI 0.700, 0.996, P = 0.045) and seven cardiovascular proteins were identified as the risk factors for DN, including CX3CL1 (OR: 1.288, 95% CI 1.012, 1.639, P = 0.039), stem cell factor (OR: 1.228, 95%CI: 1.013, 1.489, P = 0.036), tumor necrosis factor receptor 2 (OR: 1.633, 95% CI 1.141, 2.338, P = 0.007), myeloperoxidase (OR: 1.412, 95% CI 1.103, 1.808, P = 0.006), galectin-3 (OR: 1.297, 95% CI 1.095, 1.537, P = 0.003), platelet-derived growth factor subunit B (OR: 1.338, 95% CI 1.020, 1.756, P = 0.035), and interleukin-27 (OR: 1.248, 95% CI 1.033, 1.509, P = 0.022). Moreover, the reverse MR study did not observe the causal effect of DN on cardiovascular proteins. The results of sensitivity analysis suggested no significant pleiotropy and heterogeneity.

Conclusion: This MR analysis first evaluated the causal relationship between cardiovascular protein and DN at the genetic level, which could be of great significance for the prevention and treatment of DN.

Keywords: Cardiovascular proteins; Diabetic nephropathy; Genome-wide association study; Mendelian randomization.