| 丁莲富,刘洪,熊丽娟.胃食管反流与儿童哮喘的双样本双向工具变量分析[J].安徽医药,2025,29(10):1985-1989. |
| 胃食管反流与儿童哮喘的双样本双向工具变量分析 |
| Two-sample bidirectional instrumental variable analysis of gastroesophageal reflux and childhood asthma |
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| DOI:10.3969/j.issn.1009-6469.2025.10.014 |
| 中文关键词: 胃食管反流 哮喘 孟德尔随机化 因果律 遗传流行病学 儿童 |
| 英文关键词: Gastroesophageal reflux disease Asthma Mendelian randomization Causality Genetic epidemiology Child |
| 基金项目:江西省中医药管理局科技项目( 2022B079) |
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| 中文摘要: |
| 目的通过双样本双向工具变量分析探寻胃食管反流与儿童哮喘的因果关系。方法该研究的起止时间为 2024年 3月 1日至 4月 30日,从 OPEN GWAS数据库筛选出与胃食管反流、儿童哮喘相关的全基因组关联数据库( GWAS)根据双样本孟德尔随机化的要求提取工具变量,利用 R软件中的 TwoSampleMR包进行双样本双向孟德尔随机化( MR)分析,,在 5种 MR分析方法中以逆方差加权( IVW)为主分析胃食管反流与儿童哮喘的因果关系,采用 IVW和 MR-EGG中的 Cochran Q检验进行异质性分析,通过留一法、 MR-PRESSO、Egger-intercept分析研究结果的可靠性和稳定性。结果在以胃食管反流为暴露因素,儿童哮喘为结局因素的正向 MR分析中 IVW显示: OR 95%CI:1.79(1.66,1.93)P=2.033×10.51其余 4种 MR分析方法与 IVW方法结果一致, IVW和 MR-EGG中的 Cochran Q检验未见显著异质性, Egger-interce,pt分析未见水,平多效性, MR-PRESSO未见显著离群值、留一法显示研究结果稳定。在以儿童哮喘为暴露因素,胃食管反流为结局因素的反向 MR分析中 IVW显示: OR 95%CI:1.03(0.98,1.08)P=0.225,其余四种 MR分析方法与 IVW方法结果一致, IVW和 MR-EGG中的 Cochran's Q检验未见显著异质性, Egger-intercept分,析未见水平多效性, MR-PRESSO未见显著离群值、留一法显示研究结果稳定。结论从遗传学角度来看,胃食管反流与儿童哮喘的发病存在正向的因果关系,儿童哮喘与胃食管反流的发病无因果关系。 |
| 英文摘要: |
| Objective To explore the causal relationship between gastroesophageal reflux disease (GERD) and childhood asthma through a two-sample bidirectional instrumental variable analysis. Methods The duration of this study was from March 1, 2024 to April 30, 2024. Genome-wide association study (GWAS) data related to GERD and childhood asthma were retrieved from the OPENGWAS database. Instrumental variables were extracted in accordance with the requirements of two-sample Mendelian randomization(MR). The TwoSampleMR package in R software was used to conduct bidirectional MR analysis. Five MR methods were employed, withinverse variance weighting (IVW) being the primary method to analyze the causal relationship between GERD and childhood athma.Heterogeneity was assessed using the Cochran's Q test in IVW and MR-Egger, and the leave-one-out method, MR-PRESSO and Egger-intercept were used to analyze and ensure the reliability and stability of the study findings.Results In a forward MR analysis withGERD as the exposure factor and childhood asthma the outcome factor, IVW analysis indicated an odds ratio (OR) 95%CI of 1.79 (1.66, 1.93), P=2.033×10.51. The results were consistent across the other four MR analytical methods. No significant heterogeneity was detect-ed by Cochran's Q test in either IVW or MR-Egger analyses. The Egger-intercept test indicated no evidence of horizontal pleiotropy, and MR-PRESSO found no significant outliers. Results remained stable in leave-one-out sensitivity analysis. In a reverse MR analysiswith childhood asthma as the exposure factor and GERD the outcome factor, IVW analysis indicated an OR 95%CI of 1.03 (0.98,1.08), P=0.225. The results of the other four MR methods were consistent with the IVW estimates. Cochran's Q test demonstrated no signifi-cant heterogeneity in both IVW and MR-Egger analyses. The Egger-intercept analysis revealed no significant pleiotropy, while MR-PRESSO detected no outlier-driven bias. And the leave-one-out sensitivity analysis confirmed result stability.Conclusion From a ge-netic perspective, there is a significant causal relationship where GERD increases the risk of childhood asthma. However, there is nosignificant causal relationship between childhood asthma and the onset of GERD. |
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