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Causal genes for osteoporosis: Mendelian randomization analysis with multilayer xQTL data
Fei Yu1, Xiwen Wan2, Jiaxuan Qiu1
1Jiangxi Provincial Key Laboratory of Oral Diseases, Department of Stomatology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Medicine
|June 9, 2026
Summary
This study identifies 15 genes causally linked to osteoporosis using a Mendelian randomization approach. These findings offer new insights into bone metabolism and potential therapeutic targets for osteoporosis.
Area of Science:
- Genetics and Molecular Biology
- Metabolic Bone Diseases
Background:
- Osteoporosis is a heritable metabolic bone disorder with significant fracture risk.
- Identifying causal genes for osteoporosis susceptibility is crucial for understanding disease mechanisms.
Purpose of the Study:
- To identify genes with potential causal effects on osteoporosis.
- To integrate genome-wide association study (GWAS) data with multilayer molecular quantitative trait loci (xQTL) data.
- To discover novel therapeutic targets for osteoporosis.
Main Methods:
- Employed a summary-data-based Mendelian randomization (SMR) framework.
- Integrated FinnGen GWAS summary statistics with 106 xQTL datasets across multiple tissues.
- Utilized HEIDI testing for distinguishing pleiotropic associations and performed functional characterization.
Main Results:
- Identified 15 high-confidence genes with evidence of causal association with osteoporosis.
- Included established and novel candidate genes involved in bone metabolism, metabolic regulation, and signal transduction.
- Highlighted pathways in Wnt and BMP signaling, ECM organization, and metabolic processes; identified potential therapeutic agents like beta-carotene.
Conclusions:
- Provides robust genetic evidence for causal molecular regulators of osteoporosis.
- Highlights potential therapeutic targets and functional pathways for future research.
- Offers a resource for translational research in osteoporosis management.
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