Hecker Julian, Tiwari Anshul, Sharma Rinku, Mendez Kevin, Li Jiang, Begum Sofina, Chen Qingwen, Smith Albert, Celedón Juan C, Weiss Scott T, Kelly Rachel S, Lasky-Su Jessica A, Tantisira Kelan G, McGeachie Michael
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
NPJ Genom Med. 2025 Jul 17;10(1):55. doi: 10.1038/s41525-025-00510-7.
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.
哮喘给公共卫生带来了沉重负担。尽管在全基因组关联研究（GWAS）中已鉴定出一百多个遗传风险位点，但其潜在的功能机制仍知之甚少。研究组学，尤其是微小RNA（miRNA），是促进我们理解哮喘生物学途径的一种有前景的方法。在此，我们使用全基因组测序以及来自两个独立哮喘儿童队列（哥斯达黎加哮喘遗传流行病学研究（GACRS），（NCT00021840，2005 - 06 - 23）（N = 980，发现队列）和儿童哮喘管理项目（CAMP），（NCT00000575，2005 - 06 - 23）（N = 354，重复队列））的血清miRNA表达数据进行了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个在三项独立的miRNA - QTL研究中未被报道。这12个信号中的3个在CAMP中得到了重复验证。这些QTL与哮喘相关组织和细胞中的表达及剪接QTL共定位，并且与哮喘相关和血细胞性状的GWAS命中结果重叠。
