Department of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China.
Postgrad Med J. 2024 Jul 18;100(1186):555-561. doi: 10.1093/postmj/qgae019.
This study sought to investigate the causal effects of circulating C-reactive protein (CRP) level on risk of asthma and its subtypes by two-sample Mendelian randomization (MR) analysis.
We utilized single nucleotide polymorphisms (SNPs) associated with both CRP and outcomes of asthma, allergic asthma, and obesity-related asthma as genetic variables via a genome-wide summary association study (GWAS). MR analysis mainly based on the inverse variance weighted (IVW) method was performed to infer the causal relationship between exposure and outcomes. Cochran's Q test and MR-Egger regression analysis were performed to determine respectively the heterogeneity and pleiotropy among instrumental variables (IVs), and leave-one-out analysis was conducted to determine the stability of the MR results.
In our study, 42 SNPs were identified as IVs for MR analyses. According to the primary inference results by IVW methods, circulating CRP was demonstrated to be significantly associated with risk of asthma [odds ratio (OR): 1.046; 95% confidence interval (95% CI): 1.004-1.090; P = .030] and obesity-related asthma (OR: 1.072; 95% CI: 1.009-1.138; P = 0.025), whereas no distinct causality with allergic asthma was found (OR: 1.051; 95% CI: 0.994-1.112; P = .081). Sensitivity analyses indicated that there was no horizontal pleiotropy among IVs, and the MR results were proved to be robust by leave-one-out sensitivity analysis, despite the presence of heterogeneity.
The present study suggested that higher CRP might genetically predict an increased risk of developing asthma and obesity-related asthma, without causality with allergic asthma.
本研究旨在通过两样本 Mendelian 随机化（MR）分析，探讨循环 C 反应蛋白（CRP）水平对哮喘及其亚型风险的因果影响。
我们利用与 CRP 及哮喘、过敏性哮喘和肥胖相关哮喘结局均相关的单核苷酸多态性（SNP）作为遗传变量，通过全基因组汇总关联研究（GWAS）进行检测。MR 分析主要基于逆方差加权（IVW）法，推断暴露与结局之间的因果关系。采用 Cochran's Q 检验和 MR-Egger 回归分析分别评估工具变量（IVs）之间的异质性和多效性，采用逐一剔除分析评估 MR 结果的稳定性。
在本研究中，共鉴定出 42 个 SNP 作为 MR 分析的 IVs。根据 IVW 方法的主要推断结果，循环 CRP 与哮喘风险显著相关[比值比（OR）：1.046；95%置信区间（95%CI）：1.004-1.090；P = .030]和肥胖相关哮喘（OR：1.072；95% CI：1.009-1.138；P = 0.025），但与过敏性哮喘无显著因果关系（OR：1.051；95% CI：0.994-1.112；P = 0.081）。敏感性分析表明，IVs 之间不存在水平多效性，尽管存在异质性，但逐一剔除敏感性分析证明 MR 结果稳健。
本研究表明，较高的 CRP 可能与哮喘和肥胖相关哮喘的发病风险增加存在遗传相关性，与过敏性哮喘无因果关系。
