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Investigating the association between osteoporosis and acute myocardial infarction using Mendelian randomisation and
Bin Zhou1, Shaoqiang Chai1, Jiaxing Chen1
1Department of Emergency Surgery, Sixth Affiliated Hospital of Kunming Medical University, 21 Nie'er Road, Hongta District, Yuxi City, Yunnan Province, 653100, China.
Insights
Osteoporosis and acute myocardial infarction (AMI) share common genetic and molecular pathways, particularly those involving inflammation and calcium signaling. Understanding these links can inform integrated treatments for bone and heart health.
Area of Science:
- Genetics and Molecular Biology
- Cardiovascular Disease Research
- Bone Metabolism and Disease
Background:
- Osteoporosis and acute myocardial infarction (AMI) are significant health concerns in aging populations.
- The co-morbidity of osteoporosis and AMI and their underlying shared mechanisms are not well understood.
- Osteoporosis leads to bone fragility, while AMI involves myocardial ischemia and inflammation, often due to atherosclerosis.
Purpose of the Study:
- To investigate the potential causal relationship between osteoporosis and AMI.
- To identify shared molecular mechanisms and genetic underpinnings connecting these two conditions.
Main Methods:
- Utilized Mendelian Randomization (MR) analysis on large-scale Genome-Wide Association Studies (GWAS) data for osteoporosis and AMI.
- Analyzed gene expression datasets to identify differentially expressed genes (DEGs) in both conditions.
- Performed functional enrichment, immune infiltration analysis (MCPcounter), and weighted gene co-expression network analysis (WGCNA) to uncover shared biological pathways and hub genes.
Main Results:
- MR analysis confirmed a significant causal link between osteoporosis and AMI.
- Identified thousands of DEGs in both osteoporosis and AMI, with enrichment analysis pointing to immune regulation, MAPK signaling, and cancer-related pathways.
- WGCNA revealed common hub genes, and immune infiltration analysis showed distinct cellular changes in each condition, suggesting shared inflammatory processes.
Conclusions:
- Osteoporosis and AMI share significant genetic and molecular mechanisms, with inflammation and calcium signaling playing key roles.
- These findings offer novel insights into the co-morbidity of bone and cardiovascular diseases.
- Targeting shared therapeutic pathways presents a promising strategy for integrated treatment approaches to improve both bone and cardiovascular health.
Abstract:
Background: Osteoporosis and acute myocardial infarction (AMI) are major health challenges in the aging population. Osteoporosis increases bone fragility, while AMI, often due to atherosclerosis, causes myocardial ischemia and inflammation. Their co-morbidity and shared mechanisms remain unclear. Objective: To explore the causal relationship and shared molecular mechanisms between osteoporosis and AMI. Methods: GWAS data from the Risteys FinnGen R9 database (osteoporosis: 621 cases, 122,861 controls) and the IEU Open GWAS program (AMI: 20,917 cases, 461,823 controls) were analyzed using Mendelian Randomization (IVW, MR-Egger, weighted median). Gene expression datasets (GSE56815, GSE48060) were used to identify differentially expressed genes (DEGs). Functional enrichment, immune infiltration (MCPcounter), and weighted gene co-expression network analysis (WGCNA) were performed, and overlapping hub genes were identified. Results: MR analysis demonstrated a significant causal association between osteoporosis and AMI. Transcriptomic analysis revealed 2434 DEGs in osteoporosis and 2827 in AMI. Enrichment highlighted pathways including immune regulation, MAPK signaling, and cancer-related pathways. Immune infiltration showed altered monocytes and dendritic cells in osteoporosis, and cytotoxic lymphocytes and neutrophils in AMI. WGCNA identified 6 modules in osteoporosis and 11 in AMI, with 1423 common hub genes. Conclusion: Osteoporosis and AMI share genetic and molecular mechanisms, especially involving inflammation and calcium signaling. These findings provide new insights into their co-morbidity and suggest that targeting shared therapeutic pathways may support integrated strategies for improving bone and cardiovascular health.