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Causal association between vitamin D and diabetic neuropathy: a Mendelian randomization analysis
Wei Huang1,2, Lei Gu3, Jingwen Wang4
1Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014, Hangzhou, China.
Objectives:
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.
Methods:
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.
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.
Conclusions:
Our results provided no evidence to support the causal association of serum 25OHD levels with DN.
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