哮喘患儿血清microRNA表达数量性状位点与哮喘相关GWAS结果共定位。

IF 4.7 2区医学 Q1 GENETICS & HEREDITY

NPJ Genomic Medicine Pub Date : 2025-07-17 DOI:10.1038/s41525-025-00510-7

Julian Hecker, Anshul Tiwari, Rinku Sharma, Kevin Mendez, Jiang Li, Sofina Begum, Qingwen Chen, Albert Smith, Juan C Celedón, Scott T Weiss, Rachel S Kelly, Jessica A Lasky-Su, Kelan G Tantisira, Michael McGeachie

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引用次数: 0

摘要

哮喘是一个重大的公共卫生负担。尽管在全基因组关联研究（GWAS）中发现了100多个遗传风险位点，但其潜在的功能机制仍然知之甚少。研究组学，特别是microRNAs (miRNAs)，是一种很有前途的方法，有助于我们了解哮喘的生物学途径。在这里，我们使用全基因组测序和基于血清的miRNA表达数据对两个独立的哮喘儿童队列（哥斯达黎加哮喘遗传流行病学研究（GACRS），（NCT00021840, 2005-06-23）（N = 980, Discovery）和儿童哮喘管理计划（CAMP）（NCT00000575, 2005-06-23）（N = 354, Replication））进行了miRNA表达数量性状位点（miRNA- qtl）分析。我们强有力的发现分析确定了28个显著的顺式miRNA-QTL关联，其中12个在3个独立的miRNA-QTL研究中未被报道。这12个信号中的3个在CAMP中被复制。这些QTL与哮喘相关组织和细胞中的表达和剪接QTL共定位，并与哮喘相关和血细胞性状GWAS命中重叠。

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Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS results.

Asthma poses a significant public health burden. Despite identifying more than a hundred genetic risk loci in genome-wide association studies (GWAS), the underlying functional mechanisms remain poorly understood. Studying omics, especially microRNAs (miRNAs), is a promising approach to facilitate our understanding of the biological pathways of asthma. Here, we performed miRNA expression quantitative trait loci (miRNA-QTL) analyses using whole-genome sequencing and serum-based miRNA expression data from two independent cohorts of children with asthma (Genetic Epidemiology of Asthma in Costa Rica Study (GACRS), (NCT00021840, 2005-06-23) (N = 980, Discovery) and the Childhood Asthma Management Program (CAMP) (NCT00000575, 2005-06-23) (N = 354, Replication)). Our robust discovery analysis identified 28 significant cis-miRNA-QTL associations, where 12 were not reported in three independent miRNA-QTL studies. Three of these 12 signals were replicated in CAMP. The QTLs colocalize with expression and splicing QTL in asthma-relevant tissues and cells, and overlap with asthma-related and blood cell trait GWAS hits.

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来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.