Scholarlink

<p>Multiple sclerosis (MS) is an inflammatory disease that affects the central nervous system, characterized by myelin damage caused by immune dysfunction and genetic factors. Nevertheless, the role of peripheral blood and immune cells in the development of MS remains poorly defined. We employed a two-sample Mendelian randomization (MR) approach, analyzing data from 91 blood cell perturbation phenotypes and 731 immune cell traits. Causal inference was conducted using multiple robust MR techniques, including inverse variance weighting, with mediation analysis and sensitivity tests (Cochran’s Q, MR-Egger intercept, and leave-one-out analysis) performed to validate the results.The present study identified significant associations between 9 blood cell perturbation phenotypes and 34 immune cell traits with MS risk. The effect of neutrophil disturbances on MS was partially mediated by HLA-DR expression on B cells, with a mediation proportion of approximately 16.38%. Moreover, sensitivity analyses confirmed the robustness of these findings.This study suggests that specific blood cell perturbations may increase MS risk and reveals the mediating role of immune cells between blood and nervous system disturbances. In addition, we provide genetic evidence for understanding MS immune mechanisms, which could help guide the development of targeted immunotherapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Causal Effect of Blood Cell Perturbation Phenotypes on Multiple Sclerosis via Immune Mediation: A Mendelian Randomization Study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月25日

查看全文
  • Jia-Jia Yun,
  • Jin-Qiu Wang,
  • Jia-Hui Wang,
  • Zhen Wang,
  • Ya-Lei Li,
  • Yu Yang,
  • Fang-Min Chen,
  • Chao Ren

摘要

Multiple sclerosis (MS) is an inflammatory disease that affects the central nervous system, characterized by myelin damage caused by immune dysfunction and genetic factors. Nevertheless, the role of peripheral blood and immune cells in the development of MS remains poorly defined. We employed a two-sample Mendelian randomization (MR) approach, analyzing data from 91 blood cell perturbation phenotypes and 731 immune cell traits. Causal inference was conducted using multiple robust MR techniques, including inverse variance weighting, with mediation analysis and sensitivity tests (Cochran’s Q, MR-Egger intercept, and leave-one-out analysis) performed to validate the results.The present study identified significant associations between 9 blood cell perturbation phenotypes and 34 immune cell traits with MS risk. The effect of neutrophil disturbances on MS was partially mediated by HLA-DR expression on B cells, with a mediation proportion of approximately 16.38%. Moreover, sensitivity analyses confirmed the robustness of these findings.This study suggests that specific blood cell perturbations may increase MS risk and reveals the mediating role of immune cells between blood and nervous system disturbances. In addition, we provide genetic evidence for understanding MS immune mechanisms, which could help guide the development of targeted immunotherapies.