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Complex causal association between genetically predicted 731 immunocyte phenotype and osteonecrosis: a bidirectional
Wei Li1, Jing-Wen Xu2,3, Jin-Lian Chai4
1College of Traditional Chinese Medicine.
International Journal of Surgery (London, England)
|March 18, 2024
Summary
This study used Mendelian randomization to investigate the causal links between 731 immune cell phenotypes and osteonecrosis. Findings reveal a complex interplay, with specific immune cell types showing causal associations with osteonecrosis risk.
Area of Science:
- Immunology and Genetics
- Bone Biology and Disease
Background:
- Osteonecrosis is a debilitating condition with complex etiologies.
- The role of immune cells in osteonecrosis pathogenesis is increasingly recognized.
- Previous research suggests potential links between immune responses and bone death.
Purpose of the Study:
- To investigate the causal relationship between 731 immunocyte phenotypes and osteonecrosis using a Mendelian randomization approach.
- To identify specific immune cell types that may causally influence the risk of developing osteonecrosis.
- To provide evidence supporting the complex interactions between the immune system and osteonecrosis.
Main Methods:
- Utilized a two-sample Mendelian randomization (MR) design.
- Data on 731 immunocyte phenotypes and osteonecrosis were sourced from genome-wide association studies (GWAS).
- Employed inverse variable weighting (IVW) as the primary analysis, supplemented by MR-Egger, weighted mode, simple mode, and weighted median methods for robustness. Sensitivity analyses were performed to ensure data stability and feasibility.
Main Results:
- The primary MR analysis identified 8 immunocyte phenotypes positively associated with osteonecrosis and 18 negatively associated, with no evidence of heterogeneity, horizontal pleiotropy, or reverse causality.
- Reverse MR analysis indicated positive associations between osteonecrosis and 10 additional immunocyte phenotypes, and negative associations with 14 others, again without significant heterogeneity, pleiotropy, or reverse causality.
- These findings suggest a bidirectional causal relationship between specific immune cell profiles and osteonecrosis.
Conclusions:
- A complex, bidirectional causal relationship exists between numerous immune cell phenotypes and osteonecrosis.
- The immune system plays a significant, multifaceted role in the development and progression of osteonecrosis.
- This study underscores the intricate interactions between immune dysregulation and bone pathology in osteonecrosis.
