Causal association between vitamin D and diabetic neuropathy: a Mendelian randomization analysis.

Abstract

Vitamin D has been linked to diabetic neuropathy (DN) in previous epidemiological observational studies, however, their findings are inconsistent. The causal relationship between vitamin D and DN remains unknown. In this study we aim to investigate the causal association of serum 25-hydroxyvitamin D (25OHD) and DN. Based on summary statistics from publicly available genome-wide association studies (GWAS) database, we detected the genetic correlation between serum 25OHD levels and DN by a two-sample Mendelian randomization (MR) analysis. The inverse-variance weighted (IVW) method was used as the primary analysis, weighted median and MR-Egger were applied as complementary methods for MR estimates. In addition, we took sensitivity analyses including Cochran's Q test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and leave-one-out analysis to ensure that we obtained stable and reliable results. Our MR study showed no significant genetic association between serum 25OHD levels and DN (OR = 1.13, 95% CI = 0.81-1.57, P = 0.46). Furthermore, in the reverse direction analysis, we did not find a significant causal effect of DN and serum 25OHD levels (OR = 0.99, 95% CI = 0.98-1.00, P = 0.09). Results of MR-Egger, Weighted Median were consistent with those of the IVW method. The sensitivity analysis suggesting that no significant heterogeneity and genetic pleiotropy was observed. Our results provided no evidence to support the causal association of serum 25OHD levels with DN.