C-反应蛋白与哮喘之间的因果关系：两样本孟德尔随机化分析
2024/03/26
摘要
目的：本研究旨在通过两样本孟德尔随机化（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效应。
方法：我们利用与CRP和哮喘、过敏性哮喘以及与肥胖相关的哮喘结果相关的单核苷酸多态性（SNP）作为遗传变量，通过基因组范围总结关联研究（GWAS）进行MR分析。MR分析主要基于逆方差加权方法，用于推断暴露和结果之间的因果关系。 Cochran Q检验和MR-Egger回归分析分别用于确定工具变量之间的异质性和多向性，同时进行了一次性排除分析，以确定MR结果的稳定性。
结果：在我们的研究中，有42个SNP被确定为MR分析的工具变量。根据逆方差加权方法的初步推断结果，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），与肥胖相关的哮喘（OR：1.072；95% CI：1.009-1.138；P = 0.025），而与过敏性哮喘没有明显的因果关系（OR：1.051；95% CI：0.994-1.112；P = .081）。敏感性分析表明工具变量之间没有水平多向性，并且通过一次性排除敏感性分析证实了MR结果的稳健性，尽管存在异质性。
结论：本研究建议较高的CRP可能在遗传上预测哮喘和与肥胖相关的哮喘的风险增加，但与过敏性哮喘没有因果关系。
The causality between C-reactive protein and asthma: a two-sample Mendelian randomization analysis
Yong Mou, Wenhao Cao, Rujuan Wang, Xiaofan Liu, Xiuwen Yang, Jing Zhu
Abstract
Purpose: 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.
Methods: 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.
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.
Conclusion: 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.
目的：本研究旨在通过两样本孟德尔随机化（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效应。
方法：我们利用与CRP和哮喘、过敏性哮喘以及与肥胖相关的哮喘结果相关的单核苷酸多态性（SNP）作为遗传变量，通过基因组范围总结关联研究（GWAS）进行MR分析。MR分析主要基于逆方差加权方法，用于推断暴露和结果之间的因果关系。 Cochran Q检验和MR-Egger回归分析分别用于确定工具变量之间的异质性和多向性，同时进行了一次性排除分析，以确定MR结果的稳定性。
结果：在我们的研究中，有42个SNP被确定为MR分析的工具变量。根据逆方差加权方法的初步推断结果，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），与肥胖相关的哮喘（OR：1.072；95% CI：1.009-1.138；P = 0.025），而与过敏性哮喘没有明显的因果关系（OR：1.051；95% CI：0.994-1.112；P = .081）。敏感性分析表明工具变量之间没有水平多向性，并且通过一次性排除敏感性分析证实了MR结果的稳健性，尽管存在异质性。
结论：本研究建议较高的CRP可能在遗传上预测哮喘和与肥胖相关的哮喘的风险增加，但与过敏性哮喘没有因果关系。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Postgrad Med J. 2024 Mar 15:qgae019. doi: 10.1093/postmj/qgae019.)
(Postgrad Med J. 2024 Mar 15:qgae019. doi: 10.1093/postmj/qgae019.)
The causality between C-reactive protein and asthma: a two-sample Mendelian randomization analysis
Yong Mou, Wenhao Cao, Rujuan Wang, Xiaofan Liu, Xiuwen Yang, Jing Zhu
Abstract
Purpose: 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.
Methods: 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.
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.
Conclusion: 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.
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阿奇霉素诱导持续性未控制哮喘成年患者哮喘缓解：一项随机、双盲、安慰剂对照试验的二次分析
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