Causal association between 25-Hydroxyvitamin D and risk of abnormal spermatozoa: A bidirectional Mendelian randomization study

Abstract

Previous studies indicated conflicting findings regarding the association between vitamin D and abnormal spermatozoa. Herein, we assessed the causal association between circulating 25-Hydroxyvitamin D (25OHD) levels and the risk of abnormal spermatozoa by utilizing bidirectional Mendelian randomization (MR) analysis. Genome-wide association study summary statistics for 25OHD and abnormal spermatozoa were obtained from publicly accessible databases. Single nucleotide polymorphisms (SNPs) associated with 25OHD and SNPs associated with abnormal spermatozoa were used as instrumental variables (IVs) for forward MR analysis and reverse MR analysis, respectively. Inverse variance weighted (IVW) was the main MR approach, while weighted median, MR-Egger, and maximum likelihood methods were employed to supplement IVW. In addition, several sensitivity tests assessed the reliability of MR analysis. Forward MR analysis showed that elevated 25OHD levels significantly reduced abnormal spermatozoa risk (odds ratio [OR] = 0.75, 95 % confidence interval [CI]: 0.56–1.00, P = 4.98E-02), and the effect remained statistically significant after excluding SNPs associated with confounders (OR = 0.73, 95 % CI: 0.54–0.98, P = 3.83E-02) or only utilizing SNPs located near 25OHD-associated genes only as IVs (OR = 0.58, 95 % CI: 0.41–0.81, P = 1.67E-03). Reverse MR analysis indicated abnormal spermatozoa not affecting 25OHD level (P > 0.05). Sensitivity tests showed that MR analyses were not affected by heterogeneity and horizontal polytropy. Overall, the present MR study supports that elevated 25OHD levels reduce the risk of abnormal spermatozoa. Therefore, ensuring adequate vitamin D intake and maintaining stable levels of 25OHD may be effective strategies to optimize reproductive outcomes.