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Open Access 10-01-2025 | Osteoporosis | Original Article

Osteoporosis and stroke: a bidirectional mendelian randomization study

Authors: Miao He, Haochuan Yong, Zhidong Cao, Jie Li

Published in: Journal of Bone and Mineral Metabolism

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Abstract

Introduction

Numerous observational studies have identified a link between osteoporosis and stroke. However, the causal genetic relationship between these conditions remains unclear. This study employs a two-sample bidirectional Mendelian randomization (MR) approach to ascertain the causal relationship between osteoporosis and stroke.

Materials and Methods

We conducted a two-sample Mendelian randomization (MR) study to investigate the potential causal relationship between osteoporosis and stroke, including its subtypes. Genetic data for osteoporosis and stroke, along with their subtypes, were sourced from published genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) demonstrating genome-wide significance (p < 5 × 10^ − 8) and independence (r^2 < 0.001) were selected for further analysis, provided they had an F-statistic ≥ 10. The inverse-variance weighted (IVW) method was employed to evaluate causality, with results reported as odds ratios (ORs). Heterogeneity was assessed using Cochran’s Q test, while pleiotropy was tested using the MR-Egger intercept test. A leave-one-out sensitivity analysis was performed to ensure the robustness of the results.

Results

Employing the IVW method, MR Egger method, and median-weighted method, we found no significant bidirectional causal relationship between osteoporosis and stroke or its subtypes, irrespective of the inclusion of potential pleiotropic SNPs. Sensitivity analyses affirmed the reliability and stability of these findings.

Conclusion

Our study findings indicate that there is no direct causal relationship between osteoporosis and stroke or its subtypes in either direction. Based on our results, although no direct link was found, secondary effects do exist.
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Metadata
Title
Osteoporosis and stroke: a bidirectional mendelian randomization study
Authors
Miao He
Haochuan Yong
Zhidong Cao
Jie Li
Publication date
10-01-2025
Publisher
Springer Nature Singapore
Published in
Journal of Bone and Mineral Metabolism
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-025-01579-x

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