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

Abstract 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 faci...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Genomic Medicine
Online Access:https://doi.org/10.1038/s41525-025-00510-7
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Summary:Abstract 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.
ISSN:2056-7944