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The association between serum 25-hydroxyvitamin D levels and erectile dysfunction: a two-sample Mendelian randomization analysis

Abstract

Considering that vascular endothelial cell dysfunction is the pathological basis of erectile dysfunction (ED), and recognizing the beneficial effects of 25-hydroxyvitamin D (25(OH)D) on vascular endothelial cell protection, the researchers diligently investigated the causal relationship between serum 25(OH)D levels and ED. However, inconsistent clinical evidence has left the association between serum 25(OH)D levels and ED unclear. The objective of this work was to employ Mendelian randomization (MR) analysis to ascertain the potential causal relationship between serum 25(OH)D levels and ED. We conducted a two-sample MR analysis utilizing data from publicly available genome-wide association studies (GWASs). The primary analysis method for the MR analysis was the inverse-variance weighted (IVW) method, supplemented by the MR-Egger and weighted median methods. In addition, we evaluated heterogeneity with Cochran’s Q test, assessed pleiotropy using the MR-Egger intercept test, and performed a leave-one-out analysis to identify single-nucleotide polymorphisms (SNPs) with potential effects. Outliers were detected using MR-pleiotropy residual sum and outlier (MR-PRESSO). Genetically predicted serum 25(OH)D levels were not found to be causally associated with ED in IVW method (OR = 1.028, 95% CI = 0.845–1.250, P = 0.785), MR-Egger method (OR = 1.057, 95% CI = 0.782–1.430, P = 0.720), and weighted median method (OR = 1.225, 95% CI = 0.920–1.633, P = 0.165). The results of sensitivity analyses reinforced our conclusion, indicating no evidence of heterogeneity or directional pleiotropy. In summary, our findings do not substantiate a genetic-level causal link between serum 25(OH)D levels and the prevalence of ED. Nonetheless, future research, including larger MR studies, clinical trials, and additional observational studies, is essential to validate and reinforce the outcomes of our present study.

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Fig. 1: Flow chart of the study design for the Mendelian randomization study.
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Data availability

71 SNPs included in this MR analysis were included in supplemental material Table S1.

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The reader can reasonably request the MR analysis code from the corresponding authors.

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Dawei Gao, Cheng Chen, and Ziliang Wu contributed equally to this work. Dawei Gao was responsible for writing and revising the manuscript. Cheng Chen and Ziliang Wu were responsible for data collection and analysis. Huakang Li was responsible for verifying the data. Cheng Xie provided methodological guidance and suggestions for revisions to the manuscript. Bo Tang provided the research direction. All authors contributed to the article and approved the submitted version.

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Correspondence to Bo Tang.

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Gao, D., Chen, C., Wu, Z. et al. The association between serum 25-hydroxyvitamin D levels and erectile dysfunction: a two-sample Mendelian randomization analysis. Int J Impot Res (2024). https://doi.org/10.1038/s41443-024-00862-1

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