Department of Respiratory and Critical Care Medicine, Wuhan Fourth Hospital, Wuhan, Hubei Province, China.
Department of Gastroenterology, Wuhan Fourth Hospital, Wuhan, Hubei Province, China.
PLoS One. 2023 Sep 1;18(9):e0291102. doi: 10.1371/journal.pone.0291102. eCollection 2023.
This study was performed to explore the causal association between asthma and chronic obstructive pulmonary disease(COPD).
We obtained summary statistics for asthma from 408,442 Europeans in an open genome-wide association study (GWAS) from the UK Biobank to select strongly associated single nucleotide polymorphisms that could serve as instrumental variables for asthma (P < 5×10-8). Additional summary statistics for COPD were obtained from 193,638 individuals of European ancestry in the GWAS published by FinnGen. Univariable Mendelian randomization(UVMR) analysis was performed using inverse variance weighted (IVW) as the primary method of analysis. The reliability of the results was verified by multivariable MR(MVMR), reverse and replication MR analysis, and sensitivity analysis.
In the UVMR analysis, asthma increased the risk of COPD, with an odds ratio (OR) of 1.27 (95% confidence interval (CI) = 1.16-1.39, P = 5.44×10-7). Estimates were consistent in MVMR analyses by the adjustments of smoking initiation, age of smoking initiation, cigarettes per day, PM 2.5, and the combination of the above factors. In the reverse MR analysis, there was no evidence of a causal effect of COPD on asthma risk(OR = 1.02, 95% CI = 0.97-1.07, P = 0.3643). In the replication MR analysis, asthma still increased the risk of COPD. Sensitivity analyses validated the robustness of the above associations.
We found that genetically predicted asthma was positively associated with the risk of COPD. Additionally, there was no evidence that COPD increases the risk of asthma. Further clarification of this link and underlying mechanisms is needed to identify feasible measures to promote COPD prevention.
本研究旨在探索哮喘和慢性阻塞性肺疾病（COPD）之间的因果关联。
我们从英国生物库中的一项开放全基因组关联研究（GWAS）中获得了 408442 名欧洲人哮喘的汇总统计数据，以选择可作为哮喘工具变量的强关联单核苷酸多态性（P < 5×10-8）。我们从 FinnGen 发表的 GWAS 中获得了 193638 名欧洲血统 COPD 的额外汇总统计数据。采用逆方差加权（IVW）作为主要分析方法进行单变量孟德尔随机化（UVMR）分析。通过多变量 MR（MVMR）分析、反向和复制 MR 分析以及敏感性分析来验证结果的可靠性。
在 UVMR 分析中，哮喘使 COPD 的发病风险增加，比值比（OR）为 1.27（95%置信区间（CI）为 1.16-1.39，P = 5.44×10-7）。在调整吸烟起始、吸烟起始年龄、每天吸烟量、PM 2.5 以及上述因素组合后，MVMR 分析中的估计值保持一致。在反向 MR 分析中，没有证据表明 COPD 对哮喘风险有因果影响（OR = 1.02，95%CI = 0.97-1.07，P = 0.3643）。在复制 MR 分析中，哮喘仍然增加了 COPD 的发病风险。敏感性分析验证了上述关联的稳健性。
我们发现，遗传预测的哮喘与 COPD 的发病风险呈正相关。此外，没有证据表明 COPD 会增加哮喘的发病风险。需要进一步阐明这种关联和潜在机制，以确定可行的 COPD 预防措施。
