IFN-γ, SCF, MIP1b and IL-16 Were Associated with Risk of Diabetic Nephropathy: A Mendelian Randomization Study

The impact of inflammatory factors on the risk of diabetic nephropathy (DN) is inconsistent. Two-sample Mendelian randomization (MR) analyses were used to detect the causal role of inflammatory factors in DN risk.

Inflammatory factor GWAS summary data were collected from a meta-analysis including 8,293 Finnish participants, and DN information was extracted from a GWAS of 213,746 individuals from FinnGen. The MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) outlier test was used for the removal of horizontal pleiotropic outliers. Multivariable MR analysis was also used to adjust for pleiotropy.

IFN-γ [OR_IVW: 1.33; 95% CI: 1.09-1.63; p=0.005] and SCF [OR_IVW: 1.25, 1.02-1.52; p = 0.027] were associated with an increased risk of DN. MIP1b [OR_IVW: 0.92; 95% CI: 0.85-0.98; p = 0.022] and IL-16 [OR_IVW: 0.89, 0.81-0.99; p = 0.043] showed negative associations with the risk of DN. We validated our MR results with MR-PRESSO analyses. Significant horizontal pleiotropy was not found. Moreover, in the multivariable MR analysis, the associations between cytokines and DN risk remained.

Our MR results based on genetic data contribute to a better understanding of the pathogenesis of DN and provide evidence for a causal effect of inflammatory factors on DN. These findings support targeting specific inflammatory factors to alleviate DN risk.