类风湿关节炎与阻塞性肺疾病的因果关联：来自孟德尔随机化研究的证据。
Causal association of rheumatoid arthritis with obstructive lung disease: Evidence from Mendelian randomization study.
作者信息
Cao Ziqin, Li Qiangxiang, Wu Jianhuang, Li Yajia
机构信息
Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Ningxia Geriatric Disease Clinical Research Center, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750001, China; National Clinical Research Center for Geriatric Disorders of Xiangya Hospital, Central South University (Sub-center of Ningxia), Yinchuan, Ningxia Hui Autonomous Region 750001, China; Hunan People's Hospital, Geriatrics Institute of Hunan Province, Changsha, China, Changsha 410002, China.
出版信息
Heart Lung. 2023 Nov-Dec;62:35-42. doi: 10.1016/j.hrtlng.2023.05.020. Epub 2023 Jun 9.
BACKGROUND
Observational studies have found an association between rheumatoid arthritis (RA) and risk of obstructive lung disease (ORDs). However, whether RA plays a role in ORDs development remains unclear.
OBJECTIVES
This study aimed to explore the causal association of RA with ORDs.
METHODS
Both univariable and multivariable Mendelian randomization (MR) analyses were employed. Summary statistics for RA were obtained from the genome-wide association study (GWAS) meta-analysis, and the GWAS data source of ORDs, including the chronic obstructive pulmonary disease (COPD) and asthma, was accessed from the FinnGen Biobank. Causal Analysis Using Summary Effect Estimates (CAUSE) method was used to improve statistical power. multivariable and two-step mediation MR was applied to calculate the independent and mediated effects.
RESULTS
The causal estimates by univariable and CAUSE results indicated genetic predisposition to RA had an effect on the increased risk of asthma/COPD (A/C) (OR = 1.03; 95% CI: 1.02-1.04), COPD/asthma related infections (ACI) (OR = 1.02; 95% CI: 1.01-1.03) and COPD/asthma related pneumonia or pneumonia derived septicemia (ACP) (OR = 1.02; 95% CI: 1.01-1.03). Genetic predisposition to RA was significantly associated with early onset COPD (OR = 1.02; 95% CI: 1.01-1.03) and asthma (OR = 1.02; 95% CI: 1.01-1.03) risk and suggestively associated with non-allergic asthma (nAA) risk. After adjustment for confounders, independent causal effects remained for the associations of RA with risk of A/C, ACI, and ACP, as well as COPD, early-onset COPD, and asthma [total, nAA and allergic asthma (AA)] risk. Mediation analyses revealed no potential mediator.
CONCLUSION
This study indicates a causal effect of increased genetic predisposition to RA on an increased risk of ORDs, including COPD and asthma, especially early-onset COPD and nAA, and on asthma/COPD related infections, pneumonia or pneumonia derived septicemia.
背景
观察性研究发现类风湿性关节炎（RA）与阻塞性肺病（ORDs）风险之间存在关联。然而，RA是否在ORDs的发展中起作用仍不清楚。
目的
本研究旨在探讨RA与ORDs之间的因果关系。
方法
采用单变量和多变量孟德尔随机化（MR）分析。RA的汇总统计数据来自全基因组关联研究（GWAS）的荟萃分析，ORDs的GWAS数据源，包括慢性阻塞性肺疾病（COPD）和哮喘，来自芬兰生物银行。使用汇总效应估计的因果分析（CAUSE）方法来提高统计效力。应用多变量和两步中介MR来计算独立效应和中介效应。
结果
单变量和CAUSE结果的因果估计表明，RA的遗传易感性对哮喘/慢性阻塞性肺病（A/C）风险增加有影响（比值比=1.03；95%可信区间：1.02-1.04），慢性阻塞性肺病/哮喘相关感染（ACI）（比值比=1.02；95%可信区间：1.01-1.03）以及慢性阻塞性肺病/哮喘相关肺炎或肺炎源性败血症（ACP）（比值比=1.02；95%可信区间：1.01-1.03）。RA的遗传易感性与早发性慢性阻塞性肺病（比值比=1.02；95%可信区间：1.01-1.03）和哮喘（比值比=1.02；95%可信区间：1.01-1.03）风险显著相关，并与非过敏性哮喘（nAA）风险有提示性关联。在调整混杂因素后，RA与A/C、ACI和ACP风险以及慢性阻塞性肺病、早发性慢性阻塞性肺病和哮喘[总计、nAA和过敏性哮喘（AA）]风险之间的关联仍存在独立因果效应。中介分析未发现潜在中介因素。
结论
本研究表明，RA遗传易感性增加对ORDs风险增加有因果效应，包括慢性阻塞性肺病和哮喘，尤其是早发性慢性阻塞性肺病和nAA，以及对哮喘/慢性阻塞性肺病相关感染、肺炎或肺炎源性败血症。
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