Qiu Li-Juan, Yin Kang-Jia, Pan Gui-Xia, Ni Jing, Wang Bin
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.
Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China.
Front Genet. 2022 Jan 10;12:762697. doi: 10.3389/fgene.2021.762697. eCollection 2021.
Asthma is observationally associated with an increased risk of COVID-19, but the causality remains unclear. We aim to determine whether there is a casual role of asthma in susceptibility to SARS-CoV-2 infection or COVID-19 severity. Instrumental variables (IVs) for asthma and moderate-to-severe asthma were obtained from publicly available summary statistics from the most recent and largest genome-wide association study (GWAS), including 394 283 and 57 695 participants of European ancestry, respectively. The corresponding data for COVID-19 susceptibility, hospitalization and severe-disease were derived from the COVID-19 Host Genetics Initiative GWAS meta-analysis of up to 1 683 768 individuals of European descent. Causality was inferred between correlated traits by Mendelian Randomization analyses. Inverse-variance weighted method was used as the primary MR estimates and multiple alternate approaches and several sensitivity analyses were also conducted. Our MR analysis revealed no causal effects of asthma on COVID-19 susceptibility, hospitalization or severe disease, with odds ratio (OR) of 0.994 (95% CI: 0.962-1.027), 1.020 (95% CI: 0.955-1.089), and 0.929 (95% CI: 0.836-1.032), respectively. Furthermore, using genetic variants for moderate-to-severe asthma, a similar pattern of results was observed for COVID-19 susceptibility (OR: 0.988, 95% CI: 0.946-1.031), hospitalization (OR: 0.967, 95% CI: 0.906-1.031), and severe disease (OR: 0.911, 95% CI: 0.823-1.009). The association of asthma and moderate-to-severe asthma with COVID-19 was overall robust to sensitivity analyses. Genetically predicted asthma was not associated with susceptibility to, or severity of, COVID-19 disease, indicating that asthma is unlikely to be a causal factor in the development of COVID-19.
观察性研究表明，哮喘与感染新型冠状病毒肺炎（COVID-19）的风险增加有关，但因果关系仍不明确。我们旨在确定哮喘在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染易感性或COVID-19严重程度方面是否起因果作用。哮喘和中重度哮喘的工具变量（IVs）来自最近最大规模的全基因组关联研究（GWAS）的公开汇总统计数据，分别包括394283名和57695名欧洲血统参与者。COVID-19易感性、住院治疗和重症的相应数据来自COVID-19宿主遗传学倡议对多达1683768名欧洲血统个体的GWAS荟萃分析。通过孟德尔随机化分析推断相关性状之间的因果关系。采用逆方差加权法作为主要的孟德尔随机化估计方法，并进行了多种替代方法和多项敏感性分析。我们的孟德尔随机化分析显示，哮喘对COVID-19易感性、住院治疗或重症无因果效应，优势比（OR）分别为0.994（95%置信区间：0.962-1.027）、1.020（95%置信区间：0.955-1.089）和0.929（95%置信区间：0.836-1.032）。此外，使用中重度哮喘的基因变异，在COVID-19易感性（OR：0.988，95%置信区间：0.946-1.031）、住院治疗（OR：0.967，95%置信区间：0.906-1.031）和重症（OR：0.911，95%置信区间：0.823-1.009）方面观察到类似的结果模式。哮喘和中重度哮喘与COVID-19的关联在敏感性分析中总体上是稳健的。基因预测的哮喘与COVID-19疾病的易感性或严重程度无关，这表明哮喘不太可能是COVID-19发病的因果因素。
