{"title":"探索血浆代谢物在儿童哮喘中的因果作用:一项孟德尔随机研究。","authors":"Shaojie Ma, Wenjuan Hu, Yingwei Bi, Ying Han, Wei Wang, Deli Xin","doi":"10.1080/02770903.2025.2552748","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pediatric asthma (PA) is the prevailing chronic respiratory ailment in childhood. A better understanding of plasma metabolites is the goal for elucidating the molecular pathological mechanisms of PA and investigating novel therapeutic approaches.</p><p><strong>Methods: </strong>Data for PA from Genome-Wide Association Studies (GWAS) was derived from the IEU-OpenGWAS project, featuring a collection of 1400 plasma metabolites. The inverse-variance weighting (IVW) method assessed causal relationships between plasma metabolites and PA, with measures taken to mitigate horizontal pleiotropy and heterogeneity. To select instrumental variables, a genome-wide significance threshold (<i>p</i> < 5 × 10-8) was applied to ensure robust genetic instruments. A Bonferroni correction controlled for multiple testing, with statistical significance defined as <i>p</i> < 3.57 × 10-5) (0.05/1400). To further substantiate outcomes, a reverse Mendelian randomization analysis was conducted.</p><p><strong>Results: </strong>Research found 91 plasma metabolites linked to PA, ten of which showed significant associations. Of note, 20:4n6 levels (IVW: OR (95% CI) = 1.062 (1.030 to 1.094) and G/C16 (IVW: OR (95% CI) = 0.886 (0.832 to 0.943) were identified as pivotal exposure factors for PA.</p><p><strong>Conclusions: </strong>This study highlights 10 plasma metabolites that may have significant associations with PA incidence, with 20:4n6 levels and G/C16 potentially serving as valuable biomarkers for the early detection and management of PA.</p>","PeriodicalId":15076,"journal":{"name":"Journal of Asthma","volume":" ","pages":"1-14"},"PeriodicalIF":1.3000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the causal role of plasma metabolites in pediatric asthma: a Mendelian randomization study.\",\"authors\":\"Shaojie Ma, Wenjuan Hu, Yingwei Bi, Ying Han, Wei Wang, Deli Xin\",\"doi\":\"10.1080/02770903.2025.2552748\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pediatric asthma (PA) is the prevailing chronic respiratory ailment in childhood. A better understanding of plasma metabolites is the goal for elucidating the molecular pathological mechanisms of PA and investigating novel therapeutic approaches.</p><p><strong>Methods: </strong>Data for PA from Genome-Wide Association Studies (GWAS) was derived from the IEU-OpenGWAS project, featuring a collection of 1400 plasma metabolites. The inverse-variance weighting (IVW) method assessed causal relationships between plasma metabolites and PA, with measures taken to mitigate horizontal pleiotropy and heterogeneity. To select instrumental variables, a genome-wide significance threshold (<i>p</i> < 5 × 10-8) was applied to ensure robust genetic instruments. A Bonferroni correction controlled for multiple testing, with statistical significance defined as <i>p</i> < 3.57 × 10-5) (0.05/1400). To further substantiate outcomes, a reverse Mendelian randomization analysis was conducted.</p><p><strong>Results: </strong>Research found 91 plasma metabolites linked to PA, ten of which showed significant associations. Of note, 20:4n6 levels (IVW: OR (95% CI) = 1.062 (1.030 to 1.094) and G/C16 (IVW: OR (95% CI) = 0.886 (0.832 to 0.943) were identified as pivotal exposure factors for PA.</p><p><strong>Conclusions: </strong>This study highlights 10 plasma metabolites that may have significant associations with PA incidence, with 20:4n6 levels and G/C16 potentially serving as valuable biomarkers for the early detection and management of PA.</p>\",\"PeriodicalId\":15076,\"journal\":{\"name\":\"Journal of Asthma\",\"volume\":\" \",\"pages\":\"1-14\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2025-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Asthma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/02770903.2025.2552748\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Asthma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/02770903.2025.2552748","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:儿童哮喘(PA)是儿童常见的慢性呼吸系统疾病。更好地了解血浆代谢物是阐明PA的分子病理机制和探索新的治疗方法的目标。方法:全基因组关联研究(GWAS)的PA数据来自IEU-OpenGWAS项目,包含1400个血浆代谢物。反方差加权(IVW)方法评估血浆代谢物与PA之间的因果关系,并采取措施减轻水平多效性和异质性。为了选择工具变量,采用全基因组显著性阈值(p)。结果:研究发现91种血浆代谢物与PA相关,其中10种表现出显著相关性。值得注意的是,20:4n6水平(IVW: OR (95% CI) = 1.062(1.030至1.094)和G/C16 (IVW: OR (95% CI) = 0.886(0.832至0.943)被确定为PA的关键暴露因素。结论:本研究强调了10种血浆代谢物可能与PA发病率显著相关,其中20:4n6水平和G/C16可能作为PA早期检测和管理的有价值的生物标志物。
Exploring the causal role of plasma metabolites in pediatric asthma: a Mendelian randomization study.
Background: Pediatric asthma (PA) is the prevailing chronic respiratory ailment in childhood. A better understanding of plasma metabolites is the goal for elucidating the molecular pathological mechanisms of PA and investigating novel therapeutic approaches.
Methods: Data for PA from Genome-Wide Association Studies (GWAS) was derived from the IEU-OpenGWAS project, featuring a collection of 1400 plasma metabolites. The inverse-variance weighting (IVW) method assessed causal relationships between plasma metabolites and PA, with measures taken to mitigate horizontal pleiotropy and heterogeneity. To select instrumental variables, a genome-wide significance threshold (p < 5 × 10-8) was applied to ensure robust genetic instruments. A Bonferroni correction controlled for multiple testing, with statistical significance defined as p < 3.57 × 10-5) (0.05/1400). To further substantiate outcomes, a reverse Mendelian randomization analysis was conducted.
Results: Research found 91 plasma metabolites linked to PA, ten of which showed significant associations. Of note, 20:4n6 levels (IVW: OR (95% CI) = 1.062 (1.030 to 1.094) and G/C16 (IVW: OR (95% CI) = 0.886 (0.832 to 0.943) were identified as pivotal exposure factors for PA.
Conclusions: This study highlights 10 plasma metabolites that may have significant associations with PA incidence, with 20:4n6 levels and G/C16 potentially serving as valuable biomarkers for the early detection and management of PA.
期刊介绍:
Providing an authoritative open forum on asthma and related conditions, Journal of Asthma publishes clinical research around such topics as asthma management, critical and long-term care, preventative measures, environmental counselling, and patient education.