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<p>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) (<i>N</i> = 980, Discovery) and the Childhood Asthma Management Program (CAMP) (NCT00000575, 2005-06-23) (<i>N</i> = 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月17日

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  • 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

摘要

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.