Causal Effect of vitamin D on ovarian reserve function: a Mendelian randomization study

Abstract

Abstract Background 25-Hydroxyvitamin D (25(OH)D) can improve the ovarian reserve function of women; however, whether this association is causative is uncertain. Methods We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. Eligible instrumental variables (IVs) were selected according to the five assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode and the Weighted Mode. The exposure factor was 25(OH)D，and the outcome variable was Anti-mullerian hormone (AMH) 、 Follicle-stimulating hormone (FSH) 、 Luteinizing hormone (LH) and Estradiol (E2).The heterogeneity test and pleiotropic analysis were also carried out. Results Using the IVW method, results of the MR analysis showed that there was no causal association between 25(OH)D with AMH (OR = 0.978, 95%CI: 0.850-1.126 ,P = 0.758,SE=0.072) 、 FSH(OR =1.101, 95%CI: 0.797-1.208,P = 0.859,SE=0.106)、LH (OR =1.004, 95%CI: 0.753-1.339 ,P = 0.977,SE=0.147) and E2(OR = 0.903, 95%CI: 0.985-1.230 ,P 0.091,SE=0.057).In addition, the MR-Egger, the Weighted Median, the Simple Mode and the Weighted Mode methods showed consistent results. These results were confirmed to be reliable and stable by sensitivity analysis. Conclusions We found no evidence that 25(OH)D was causally associated with the ovarian reserve function of women