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08-06-2024 | Original Article

The impact of bone mineral density on the risk of falling: evidence from genetic correlation and Mendelian randomization analysis

Authors: Rumeng Mao, Luyao Peng, Youqian Zhang, Lin Li, Yanrui Ren

Published in: Endocrine

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Abstract

Background

Falls are the most common consequence of low bone mineral density (BMD). However, due to limitations inherent in observational studies, the causal relationship between the two remains unestablished.

Methods

This study utilized Mendelian Randomization (MR) analysis to explore the causal relationship between BMD and the risk of falling, incorporating linkage disequilibrium score (LDSC) regression for genetic correlation assessment. The primary method was inverse-variance weighted (IVW), supplemented with sensitivity analyses and the causal analysis using summary effect estimates (CAUSE) to address heterogeneity and pleiotropy biases.

Results

LDSC analysis indicated significant genetic correlations between BMD at various sites and falling risk (rg range: −0.82 to 0.76, all P < 0.05). IVW analysis, with False Discovery Rate (FDR) correction, showed a protective causal effect of total body BMD (OR = 0.85, 95% CI 0.82–0.88, P = 7.63 × 10−17, PFDR = 1.91 × 10−16), femoral neck BMD (OR = 0.81, 95% CI 0.75–0.88, P = 3.33 × 10−7, PFDR = 5.55 × 10−7), lumbar spine BMD (OR = 0.85, 95% CI 0.79–0.91, P = 9.56 × 10−7, PFDR = 1.20 × 10−6), and heel BMD (OR = 0.82, 95% CI 0.79–0.81, P = 1.69 × 10−39, PFDR = 8.45 × 10−39) on falling risk. No causal relationship was found for forearm BMD (OR = 1.02, 95% CI 0.94–1.11, P = 0.64, PFDR = 0.64). Replication datasets and CAUSE analysis provided causal evidence consistent with the main findings.

Conclusion

The study established a causal relationship between BMD at four different sites and the risk of falling, highlighting potential areas for targeted prevention strategies.
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Metadata
Title
The impact of bone mineral density on the risk of falling: evidence from genetic correlation and Mendelian randomization analysis
Authors
Rumeng Mao
Luyao Peng
Youqian Zhang
Lin Li
Yanrui Ren
Publication date
08-06-2024
Publisher
Springer US
Published in
Endocrine
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-024-03904-2
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