Genetically predicted immune cell mediate the association between plasma lipidomics and osteomyelitis
Xujin Wu1, Xiao Zhang1, Wei Xu1
1Department of Orthopedics, The Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou, 215004, Jiangsu, China.
Background:
Osteomyelitis is a disease with a complex etiology and a high recurrence rate, which causes significant distress to both patients and physicians. There is currently no clear understanding of the factors that influence the progression of osteomyelitis. Previously, only small-sample observational studies have demonstrated an association between osteomyelitis, plasma lipidomics and immune cell characteristics. The objective of this study is to analyze the causal relationship between lipidomics and osteomyelitis by Mendelian randomization and to determine the mediating role of immune cells in this process.
Methods:
This study validated the causal relationship between osteomyelitis and 179 lipid species by two-sample Mendelian randomization analysis using publicly available genetic data. To ensure the reliability of the findings, this study employed both sensitivity analysis and inverse Mendelian randomization analysis. Furthermore, this study used two-step Mendelian to quantify the proportion of immune cell characteristics mediated lipidomics in osteomyelitis.
Result:
After rigorous screening of instrumental variables, and multiple Mendelian randomization methods, this study identified a causal relationship between 5 lipid species and 20 immune cell traits and osteomyelitis. Through a comprehensive analysis of causality, this study identified an increased risk of osteomyelitis with increased Diacylglycerol (d40:2) levels (inverse variance-weighted method, [OR] per SD increase in osteomyelitis = 1.147 [95% CI 1.46-1.276], P = 0.004) and 10.665% was mediated through CD27 on IgD-CD38dim. However, It has been demonstrated that an increase in Diacylglycerol (16:1_18:1) levels (inverse variance-weighted method, [OR] per SD increase in osteomyelitis = 0.887 [95% CI 0.800-0.983], P = 0.023) reduces the risk of osteomyelitis and 6.640% was mediated through CD20 on IgD+ .
Conclusion:
This study reveals that increased Ceramide (d40:2) levels increase the risk of developing osteomyelitis, with CD27 on IgD-CD38dim mediating part of the effect. At the same time, Diacylglycerol (16:1_18:1) levels were increased and would reduce the risk of developing osteomyelitis, partly mediated through CD20 on IgD+ . This study further reveals the factors affecting the development and progression of osteomyelitis and provides new ideas for the treatment of osteomyelitis.
