炎症介导的MRI定义体成分肥胖轴对慢性阻塞性肺疾病、哮喘和过敏性鼻炎的因果效应：一项孟德尔随机化研究。
Inflammation-Mediated Causal Effects of MRI-Defined Body-Composition Obesity Axes on Chronic Obstructive Pulmonary Disease, Asthma, and Allergic Rhinitis: A Mendelian Randomization Study.
文献信息
| PMID | 42836120 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Bo Zeng |
| 作者单位 | Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, People's Republic of China. |
| 期刊 | International journal of chronic obstructive pulmonary disease |
| SCI 分区 | Q1 |
| IF | 3.9 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 鼻科 |
中文摘要
背景： 肥胖具有异质性；传统人体测量指标综合了脂肪分布、异位脂肪沉积和肌肉体积，限制了对慢性气道疾病的精细因果推断。我们使用四个MRI定义的肥胖轴来评估其对慢性阻塞性肺疾病（COPD）、哮喘和过敏性鼻炎（AR）的因果效应，并评估循环炎症蛋白的中介作用。
方法： 为四个MRI定义的肥胖轴选择遗传工具变量。两样本孟德尔随机化（MR）以逆方差加权法为主要方法，并辅以敏感性分析和错误发现率校正。使用非重叠的FinnGen结局数据进行发现，并在全球生物银行荟萃分析计划中对COPD和哮喘、在百万退伍军人计划中对AR进行重复验证，随后进行荟萃分析。两步MR评估炎症蛋白的中介作用。
结果： 遗传预测的全身肥胖轴与COPD（OR = 1.125，95% CI：1.012-1.250）、哮喘（OR = 1.533，95% CI：1.426-1.647）和AR（OR = 1.624，95% CI：1.328-1.987）风险增加相关。下半身脂肪轴与COPD（OR = 1.192，95% CI：1.088-1.306）和哮喘（OR = 1.135，95% CI：1.052-1.224）风险较高相关。其他肥胖轴未观察到因果证据。重复验证和荟萃分析大体支持这些发现，但全身肥胖与AR除外，其合并证据处于临界水平（P = 0.055）。中介分析确定了17条候选炎症通路，其中10条显著。FLT3L介导了全身肥胖对COPD效应的18.17%，CXCL5介导了其对哮喘效应的3.78%。CD40L受体和LIFR分别介导了下半身脂肪-哮喘效应的5.59%和12.65%，而CD40L受体、CXCL10、IL-12B、OPG和TNFRSF9在选定通路中显示出抑制性中介作用。
结论： MRI定义的肥胖轴提供了遗传证据，支持通过炎症中介通路与气道疾病存在潜在因果关联。
英文摘要
BACKGROUND: Obesity is heterogeneous; conventional anthropometric measures combine fat distribution, ectopic fat deposition, and muscle volume, limiting refined causal inference for chronic airway diseases. We used four magnetic resonance imaging (MRI)-defined obesity axes to assess their causal effects on chronic obstructive pulmonary disease (COPD), asthma, and allergic rhinitis (AR), and to evaluate mediation by circulating inflammatory proteins.
METHODS: Genetic instruments were selected for four MRI-defined obesity axes. Two-sample Mendelian randomization (MR) used inverse-variance weighting as the primary method, with complementary sensitivity analyses and false discovery rate correction. Non-overlapping FinnGen outcome data were used for discovery, with replication in the Global Biobank Meta-analysis Initiative for COPD and asthma and the Million Veteran Program for AR, followed by meta-analysis. Two-step MR assessed inflammatory protein mediation.
RESULTS: Genetically predicted general obesity axis was associated with increased risks of COPD (OR = 1.125, 95% CI: 1.012-1.250), asthma (OR = 1.533, 95% CI: 1.426-1.647), and AR (OR = 1.624, 95% CI: 1.328-1.987). The lower-body fat axis was associated with higher risks of COPD (OR = 1.192, 95% CI: 1.088-1.306) and asthma (OR = 1.135, 95% CI: 1.052-1.224). No causal evidence was observed for the other obesity axes. Replication and meta-analysis largely supported these findings, except for general obesity and AR, which showed borderline pooled evidence (P = 0.055). Mediation analysis identified 17 candidate inflammatory pathways, of which 10 were significant. FLT3L mediated 18.17% of the effect of general obesity on COPD, and CXCL5 mediated 3.78% of its effect on asthma. CD40L receptor and LIFR mediated 5.59% and 12.65% of the lower-body fat-asthma effect, respectively, whereas CD40L receptor, CXCL10, IL-12B, OPG, and TNFRSF9 showed suppressive mediation in selected pathways.
CONCLUSION: MRI-defined obesity axes provided genetic evidence supporting potential causal associations with airway diseases through inflammatory mediation pathways.