Exploring the Causal Relationship Between Frailty and Chronic Obstructive Pulmonary Disease: Insights From Bidirectional Mendelian Randomization and Mediation Analysis.

IF 3.1 3区医学 Q2 RESPIRATORY SYSTEM International Journal of Chronic Obstructive Pulmonary Disease Pub Date : 2025-01-25 eCollection Date: 2025-01-01 DOI:10.2147/COPD.S501635

Zewen Cheng, Jian Wu, Chun Xu, Xiaokun Yan

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Abstract

Background: Observational studies have underscored a robust association between frailty and chronic obstructive pulmonary disease (COPD), yet the causality remains equivocal.

Methods: This study employed bidirectional two-sample Mendelian randomization (MR) analysis. Univariable MR investigated the causal relationship between frailty and COPD. Genetic correlation was assessed using linkage disequilibrium score (LDSC) regression. Multivariable MR and mediation analysis explored the influence of various confounders and their mediating effects. The primary analytic approach was inverse variance weighted (IVW).

Results: LDSC analysis revealed moderate genetic correlations between frailty and Global Biobank Meta-Analysis Initiative (GBMI) COPD (r_g = 0.643, P = 6.66×10^-62) as well as FinnGen COPD (r_g = 0.457, P = 8.20×10^-28). IVW analysis demonstrated that frailty was associated with increased risk of COPD in both the GBMI cohort (95% CI, 1.475 to 2.158; P = 2.40×10^-9) and the FinnGen database (1.411 to 2.434; 9.02×10^-6). Concurrently, COPD was identified as a susceptibility factor for frailty (P < 0.05). These consistent findings persisted after adjustment for potential confounders in MVMR. Additionally, mediation analysis revealed that walking pace mediated 19.11% and 15.40% of the impact of frailty on COPD risk, and 17.58% and 23.26% of the effect of COPD on frailty risk in the GBMI and FinnGen cohorts, respectively.

Conclusion: This study has strengthened the current evidence affirming a reciprocal causal relationship between frailty and COPD, highlighting walking pace as a pivotal mediator.

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探索虚弱和慢性阻塞性肺疾病之间的因果关系：双向孟德尔随机化和中介分析的见解。

背景：观察性研究强调了虚弱和慢性阻塞性肺疾病（COPD）之间的强大关联，但因果关系仍然模棱两可。方法：采用双向双样本孟德尔随机化（MR）分析。单变量MR研究了虚弱和COPD之间的因果关系。遗传相关性评估采用连锁不平衡评分（LDSC）回归。多变量MR和中介分析探讨了各种混杂因素的影响及其中介效应。主要分析方法是逆方差加权（IVW）。结果：LDSC分析显示，衰弱与全球生物银行meta分析倡议（GBMI） COPD （rg = 0.643, P = 6.66×10-62）和FinnGen COPD （rg = 0.457, P = 8.20×10-28）之间存在中度遗传相关性。IVW分析显示，在GBMI队列中，虚弱与COPD风险增加相关(95% CI, 1.475 - 2.158；P = 2.40×10-9)和FinnGen数据库(1.411 ~ 2.434；9.02×10 - 6)。同时，COPD被确定为虚弱的易感因素（P < 0.05）。在调整了MVMR的潜在混杂因素后，这些一致的发现仍然存在。此外，中介分析显示，在GBMI和FinnGen队列中，步行速度分别介导了19.11%和15.40%的衰弱对COPD风险的影响，17.58%和23.26%的COPD对衰弱风险的影响。结论：这项研究加强了目前的证据，确认虚弱和COPD之间存在相互的因果关系，强调步行速度是一个关键的中介。

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来源期刊

International Journal of Chronic Obstructive Pulmonary Disease RESPIRATORY SYSTEM-

CiteScore

4.80

自引率

10.70%

发文量

372

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed journal of therapeutics and pharmacology focusing on concise rapid reporting of clinical studies and reviews in COPD. Special focus will be given to the pathophysiological processes underlying the disease, intervention programs, patient focused education, and self management protocols. This journal is directed at specialists and healthcare professionals