Department of Anorectal, the Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China.
Graduate School, Hunan University of Traditional Chinese Medicine, Changsha, China.
Front Immunol. 2024 Sep 2;15:1416562. doi: 10.3389/fimmu.2024.1416562. eCollection 2024.
To evaluate the causal relationship between lipids and ulcerative colitis (UC) through Mendelian Randomization (MR), and to further investigate the involvement of immune cells in mediating this process.
Utilizing summary statistics from genome-wide association studies (GWAS) of individuals with European ancestry, we analyzed the causal link between 179 lipid types and UC (2,569 UC cases and 453,779 controls) through Two-sample Mendelian randomization (2SMR) and Bayesian-weighted MR (BWMR). Based on this, a mediation screening of 731 immune cell phenotypes was conducted to identify exposure and mediator factors. Lastly, the role and proportion of immune cells in mediating the causal effects of lipids on UC were assessed via reverse MR (RMR) and two-step MR.
The results of MR showed that there was a causal relationship between the six genetically predicted lipid types and UC (P <0.05), and the four immune cell phenotypes were identified as mediators of the association between lipids and UC. Notably, Phosphatidylcholine (PC) (16:0_0:0) served as the exposure factor, and myeloid cells CD11b on CD33+ HLA DR+ CD14dim acted as the mediator. Mediation analysis showed that CD11b on CD33+ HLA DR+ CD14dim had a mediation effect of -0.0205 between PC (16:0_0:0) and UC, with the mediation effect ratio at 15.38%.
Our findings elucidate the causal effect of lipids on UC and identify the significant mediating role of myeloid cells CD11b on CD33+ HLA DR+ CD14dim in regulating UC through PC (16:0_0:0), offering new pathways and strategies for UC clinical treatment.
通过孟德尔随机化（MR）评估脂质与溃疡性结肠炎（UC）之间的因果关系，并进一步研究免疫细胞在介导这一过程中的作用。
利用欧洲血统个体的全基因组关联研究（GWAS）的汇总统计数据，我们通过两样本孟德尔随机化（2SMR）和贝叶斯加权 MR（BWMR）分析了 179 种脂质类型与 UC（2569 例 UC 病例和 453779 例对照）之间的因果关系。在此基础上，对 731 种免疫细胞表型进行了中介筛选，以确定暴露和中介因素。最后，通过反向 MR（RMR）和两步 MR 评估免疫细胞在介导脂质对 UC 的因果效应中的作用和比例。
MR 结果表明，六种遗传预测的脂质类型与 UC 之间存在因果关系（P<0.05），并确定了四种免疫细胞表型作为脂质与 UC 之间关联的中介。值得注意的是，磷酸胆碱（PC）（16:0_0:0）作为暴露因素，CD33+ HLA DR+ CD14dim 上的髓样细胞 CD11b 作为中介。中介分析表明，PC（16:0_0:0）和 UC 之间，CD33+ HLA DR+ CD14dim 上的 CD11b 具有-0.0205 的中介效应，其中介效应比为 15.38%。
本研究阐明了脂质对 UC 的因果影响，并确定了髓样细胞 CD11b 对 CD33+ HLA DR+ CD14dim 通过 PC（16:0_0:0）调节 UC 的显著中介作用，为 UC 的临床治疗提供了新的途径和策略。
