Causal Relationships Between Immune Cell Traits, Plasma Metabolites, and Asthma: A Two-Step, Two-Sample Mendelian Randomization Study

IF 2.3 4区医学 Q3 RESPIRATORY SYSTEM

Clinical Respiratory Journal Pub Date : 2025-06-23 DOI:10.1111/crj.70097

Zhuozheng Hu, Peihao Xu, Jiajun Wu, Weijun Zhou, Yajie Zhou, Lei Xie, Wenxiong Zhang, Yong Cheng

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引用次数: 0

Abstract

Background

Considerable evidence suggests a strong link between immune cell traits (ICTs) and asthma development via plasma metabolites (PMs), but the causality between ICTs and asthma is still unclear, mainly due to issues like selection bias. Our research was designed to investigate the causality between ICTs, PMs, and asthma and to provide a clearer explanation of these relationships.

Methods

Utilizing the GWAS database, this study employed a two-step, two-sample Mendelian randomization (MR) approach and the inverse variance weighted (IVW) method to investigate the causality between ICTs and asthma, as well as between PMs and asthma. Lastly, we calculated the mediated proportion of PMs as mediators in the link between ICTs and asthma.

Results

Excluding heterogeneity and pleiotropy, MR analysis identified 13 ICTs (CD14 on CD33br HLA DR+ CD14dim, etc.) and asthma causality, and no reverse causality was observed. In addition, 27 PMs (androsterone sulfate levels, succinate levels, etc.) were also causally associated with asthma. Mediate MR indicated −9.81% (−1.2%, −18.4%) of the effect of CD24 on IgD+ CD38br on asthma is mediated by S-methylcysteine sulfoxide levels, with a mediated effect value (p = 0.006) is 0.003 (0.0004, 0.006); 21.4% (6.2%, −36.6%) of the effect of CD3 on CD28+ CD4+ on asthma is mediated by 1-myristoyl-2-arachidonoyl-GPC (14:0/20:4) levels, with a mediated effect value (p = 0.025) is 0.004 (0.001, 0.007).

Conclusions

We identified two pathways by which ICTs can impact asthma through PMs, which might help in identifying potential targets for personalized treatment approaches.

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免疫细胞特征、血浆代谢物和哮喘之间的因果关系：一项两步、两样本孟德尔随机研究

大量证据表明，免疫细胞特征（ict）与哮喘通过血浆代谢物（PMs）之间存在密切联系，但ict与哮喘之间的因果关系仍不清楚，主要是由于选择偏差等问题。我们的研究旨在调查信息通信技术、pmms和哮喘之间的因果关系，并为这些关系提供更清晰的解释。方法利用GWAS数据库，采用两步、两样本孟德尔随机化（MR）方法和逆方差加权（IVW）方法，探讨ict与哮喘、pmms与哮喘之间的因果关系。最后，我们计算了pm在ict和哮喘之间的关联中作为中介的中介比例。结果排除异质性和多效性，MR分析确定了13个ict （CD14 on CD33br HLA DR+ CD14dim等）与哮喘的因果关系，未发现反向因果关系。此外，27种PMs（硫酸雄酮水平、琥珀酸水平等）也与哮喘有因果关系。介导MR提示- 9.81% (- 1.2%,- 18.4%)CD24对IgD+ CD38br对哮喘的作用是由s -甲基半胱氨酸亚砜水平介导的，介导效应值（p = 0.006）为0.003 (0.0004,0.006)；21.4%（6.2%,−36.6%）的CD3对CD28+ CD4+对哮喘的影响是由1-肉豆肉酰基-2-花生四烯酰基- gpc（14:0/20:4）水平介导的，介导效应值（p = 0.025）为0.004（0.001,0.007）。我们确定了信息通信技术通过pmms影响哮喘的两种途径，这可能有助于确定个性化治疗方法的潜在目标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Respiratory Journal 医学-呼吸系统

CiteScore

3.70

自引率

0.00%

发文量

104

审稿时长

>12 weeks

期刊介绍： Overview Effective with the 2016 volume, this journal will be published in an online-only format. Aims and Scope The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic. We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including: Asthma Allergy COPD Non-invasive ventilation Sleep related breathing disorders Interstitial lung diseases Lung cancer Clinical genetics Rhinitis Airway and lung infection Epidemiology Pediatrics CRJ provides a fast-track service for selected Phase II and Phase III trial studies. Keywords Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)