PDF(Pubmed)
Abstract：
OBJECTIVE: The objective of this study is to elucidate the causal association between asthma and alopecia areata (AA) through the application of Mendelian randomization (MR) analysis, leveraging summary data from genome-wide association studies (GWAS). Additionally, it explores potential mediating factors.
METHODS: Mendelian randomization (MR) analysis was employed to investigate the causal relationship between asthma and AA using genetic instrumental variables (IVs) for asthma, 91 circulating inflammatory proteins, and AA extracted from large-scale GWAS. The primary analytical approach utilized the inverse-variance weighted (IVW) method, supplemented by weighted median and MR-Egger methods to assess robustness. Tests for heterogeneity and pleiotropy were conducted to ensure result reliability. Furthermore, the study examined the mediating role of circulating inflammatory proteins in the asthma-AA relationship.
RESULTS: The findings revealed an increased risk of AA among asthma patients (odds ratio (OR) = 14.070; 95% confidence interval (CI) = 1.410-140.435; P = 0.024). Interleukin-33 (IL-33) emerged as a significant mediator in the asthma-AA relationship, explaining 13.1% of the mediation effect. Bidirectional Mendelian randomization analyses did not establish a causal effect of AA on asthma occurrence.
CONCLUSIONS: This study, utilizing Mendelian Randomization, elucidates the causal link between asthma and AA, highlighting the mediating role of IL-33. These findings underscore the importance of considering AA risk in asthma management and offer insights for potential therapeutic strategies targeting IL-33. Future research should explore additional biomarkers and mediating mechanisms between asthma and AA to enhance treatment approaches and patient quality of life.
METHODS: Mendelian randomization (MR) analysis was employed to investigate the causal relationship between asthma and AA using genetic instrumental variables (IVs) for asthma, 91 circulating inflammatory proteins, and AA extracted from large-scale GWAS. The primary analytical approach utilized the inverse-variance weighted (IVW) method, supplemented by weighted median and MR-Egger methods to assess robustness. Tests for heterogeneity and pleiotropy were conducted to ensure result reliability. Furthermore, the study examined the mediating role of circulating inflammatory proteins in the asthma-AA relationship.
RESULTS: The findings revealed an increased risk of AA among asthma patients (odds ratio (OR) = 14.070; 95% confidence interval (CI) = 1.410-140.435; P = 0.024). Interleukin-33 (IL-33) emerged as a significant mediator in the asthma-AA relationship, explaining 13.1% of the mediation effect. Bidirectional Mendelian randomization analyses did not establish a causal effect of AA on asthma occurrence.
CONCLUSIONS: This study, utilizing Mendelian Randomization, elucidates the causal link between asthma and AA, highlighting the mediating role of IL-33. These findings underscore the importance of considering AA risk in asthma management and offer insights for potential therapeutic strategies targeting IL-33. Future research should explore additional biomarkers and mediating mechanisms between asthma and AA to enhance treatment approaches and patient quality of life.
摘要：
目的：本研究的目的是通过孟德尔随机化（MR）分析来阐明哮喘与斑秃（AA）之间的因果关系。利用来自全基因组关联研究(GWAS)的汇总数据。此外,它探索了潜在的中介因素。
方法：采用孟德尔随机化（MR）分析，使用哮喘的遗传工具变量（IVs）研究哮喘与AA之间的因果关系，91个循环炎性蛋白，从大规模GWAS中提取AA。主要的分析方法采用了逆方差加权(IVW)方法，辅以加权中位数和MR-Egger方法评估稳健性。进行了异质性和多效性测试，以确保结果的可靠性。此外，本研究探讨了循环炎症蛋白在哮喘-AA关系中的介导作用.
结果：结果显示哮喘患者患AA的风险增加（比值比（OR）=14.070；95％置信区间（CI）=1.410-140.435；P=0.024）。白细胞介素-33（IL-33）作为哮喘-AA关系的重要介质出现，解释了13.1%的调解效果。双向孟德尔随机化分析未确定AA对哮喘发生的因果关系。
结论：这项研究，利用孟德尔随机化，阐明哮喘和AA之间的因果关系，强调IL-33的中介作用。这些发现强调了在哮喘管理中考虑AA风险的重要性，并为针对IL-33的潜在治疗策略提供了见解。未来的研究应该探索哮喘和AA之间的其他生物标志物和介导机制，以提高治疗方法和患者的生活质量。
方法：采用孟德尔随机化（MR）分析，使用哮喘的遗传工具变量（IVs）研究哮喘与AA之间的因果关系，91个循环炎性蛋白，从大规模GWAS中提取AA。主要的分析方法采用了逆方差加权(IVW)方法，辅以加权中位数和MR-Egger方法评估稳健性。进行了异质性和多效性测试，以确保结果的可靠性。此外，本研究探讨了循环炎症蛋白在哮喘-AA关系中的介导作用.
结果：结果显示哮喘患者患AA的风险增加（比值比（OR）=14.070；95％置信区间（CI）=1.410-140.435；P=0.024）。白细胞介素-33（IL-33）作为哮喘-AA关系的重要介质出现，解释了13.1%的调解效果。双向孟德尔随机化分析未确定AA对哮喘发生的因果关系。
结论：这项研究，利用孟德尔随机化，阐明哮喘和AA之间的因果关系，强调IL-33的中介作用。这些发现强调了在哮喘管理中考虑AA风险的重要性，并为针对IL-33的潜在治疗策略提供了见解。未来的研究应该探索哮喘和AA之间的其他生物标志物和介导机制，以提高治疗方法和患者的生活质量。
