Investigating the causal association between heme oxygenase-1 and asthma: A bidirectional two-sample Mendelian randomization analysis in a European population

IF 3.9 2区医学 Q2 ALLERGY

World Allergy Organization Journal Pub Date : 2024-10-24 DOI:10.1016/j.waojou.2024.100987

Wen Liu , Zhen Liu , Xiao-di Sun , Zeng-qiang Liu , Yuan-yuan Dong , Shi Qiu

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引用次数: 0

Abstract

Background

The association between heme oxygenase-1 (HO-1) and asthma has been a subject of debate in both observational and experimental studies. We aimed to evaluate the potential causal relationship between HO-1 and asthma.

Materials and methods

A bidirectional two-sample Mendelian randomization (TSMR) study was conducted to examine the causal relationship between HO-1 and asthma. In the forward Mendelian randomization (MR) analyses, HO-1 was considered as the exposure, while asthma as the outcome. Conversely, in the reverse MR analyses, asthma was regarded as the exposure, and HO-1 as the outcome. Data for HO-1 and asthma were obtained from publicly accessible genome-wide association studies (GWAS). These causal relationships were identified through 5 MR methods, namely MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, and weighted mode. Additionally, sensitivity tests were conducted to assess the robustness of MR study. Finally, additional asthma datasets and childhood asthma were selected to validate the findings.

Results

In the forward MR analyses, according to the IVW method, genetically predicted HO-1 displays a negative correlation with the risk of asthma (OR 0.947, 95% CI 0.905–0.990). It was not found any SNP overly sensitive or disproportionately responsible for the outcome. No evidence of heterogeneity and pleiotropy between SNPs was observed. Genetically predicted asthma was not associated with HO-1 in reverse MR analyses using the IVW method. The same results were validated in additional asthma datasets and in childhood asthma.

Conclusion

The results of MR analysis revealed heme oxygenase-1 as a protective factor for asthma.

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调查血红素加氧酶-1与哮喘之间的因果关系：欧洲人群中的双向双样本孟德尔随机分析

背景血红素加氧酶-1（HO-1）与哮喘之间的关系一直是观察性和实验性研究中争论的主题。我们的目的是评估 HO-1 与哮喘之间的潜在因果关系。材料与方法为研究 HO-1 与哮喘之间的因果关系，我们进行了一项双向双样本孟德尔随机化（TSMR）研究。在正向孟德尔随机分析（MR）中，HO-1 被认为是暴露因子，而哮喘被认为是结果因子。相反，在反向孟德尔随机分析中，哮喘被视为暴露，而 HO-1 被视为结果。HO-1和哮喘的数据来自公开的全基因组关联研究（GWAS）。这些因果关系是通过 5 种 MR 方法确定的，即 MR-Egger、加权中位数、逆方差加权（IVW）、简单模式和加权模式。此外，还进行了敏感性测试，以评估 MR 研究的稳健性。结果在正向 MR 分析中，根据 IVW 方法，基因预测的 HO-1 与哮喘风险呈负相关（OR 0.947，95% CI 0.905-0.990）。没有发现任何 SNP 对结果过于敏感或不成比例。没有发现 SNP 之间存在异质性和多义性。在使用 IVW 方法进行的反向 MR 分析中，遗传预测的哮喘与 HO-1 无关。结论 MR 分析结果显示血红素加氧酶-1 是哮喘的保护因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Allergy Organization Journal Immunology and Microbiology-Immunology

CiteScore

9.10

自引率

5.90%

发文量

审稿时长

9 weeks

期刊介绍： The official pubication of the World Allergy Organization, the World Allergy Organization Journal (WAOjournal) publishes original mechanistic, translational, and clinical research on the topics of allergy, asthma, anaphylaxis, and clincial immunology, as well as reviews, guidelines, and position papers that contribute to the improvement of patient care. WAOjournal publishes research on the growth of allergy prevalence within the scope of single countries, country comparisons, and practical global issues and regulations, or threats to the allergy specialty. The Journal invites the submissions of all authors interested in publishing on current global problems in allergy, asthma, anaphylaxis, and immunology. Of particular interest are the immunological consequences of climate change and the subsequent systematic transformations in food habits and their consequences for the allergy/immunology discipline.