Immune cell-mediated causal relationship between plasma metabolites and knee osteoarthritis:a Mendelian randomization study
10.7644/j.issn.1674-9960.2024.10.008
- VernacularTitle:免疫细胞介导的血浆代谢物与膝骨关节炎的因果关系:孟德尔随机化研究
- Author:
Zhenyu WANG
1
;
Hongmei ZHANG
;
Lin JING
;
Qi YAN
;
Jixiang TANG
;
Qirui GE
Author Information
1. 中国中医科学院望京医院,北京 100102
- Keywords:
knee osteoarthritis;
plasma metabolites;
immune traits;
causal inference;
Mendelian randomization;
media-tion analysis
- From:
Military Medical Sciences
2024;48(10):778-785
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate both the causal relationship between plasma metabolites and the risk of knee osteoarthritis(KOA)and the potential mediating or masking effect of immune cells using Mendelian randomization(MR)systems.Methods The GWAS data on 1400 plasma metabolites,731 immune cell traits and KOA was retrieved from the genome-wide association study(GWAS)database.Two-way MR analysis was used to evaluate the causal relationship between plasma metabolism and KOA.Two-step mediation MR analysis was conducted to evaluate immune cell traits that might have mediating or masking effects.Results After sensitivity analysis and screening,65 plasma metabolites and 35 immune cell traits were found to have causal relationships with KOA(P＜0.05).Mediation analysis found that CD45RA+CD28-CD8br％CD8br had a mediating effect in the causal relationship between three metabolites(2-hydroxyhi-ppurate,X-07765,X-23739)and the risk of KOA.2-hydroxyhippurate(salicylic acid)exerted a masking effect,and the effect ratio was 0.0412.Conclusion A variety of plasma metabolites and immune cell traits are causally related to KOA,which should not be regarded as a simple degenerative joint disease.The protective effect of salicylic acid against KOA may be weakened by its role in inducing the differentiation of Treg cells,which is worthy of more studies.
