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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Nature Portfolio
2025-07-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-025-00510-7 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Julian Hecker |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1e8bb948342f46ffb42b689e50a7e31b |
| institution | DOAJ |
| issn | 2056-7944 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj-art-1e8bb948342f46ffb42b689e50a7e31b2025-08-20T03:05:16ZengNature Portfolionpj Genomic Medicine2056-79442025-07-0110111010.1038/s41525-025-00510-7Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS resultsJulian Hecker0Anshul Tiwari1Rinku Sharma2Kevin Mendez3Jiang Li4Sofina Begum5Qingwen Chen6Albert Smith7Juan C. Celedón8Scott T. Weiss9Rachel S. Kelly10Jessica A. Lasky-Su11Kelan G. Tantisira12Michael McGeachie13Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolDepartment of Molecular Physiology and Biophysics, Vanderbilt UniversityChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public HealthDivision of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh, University of PittsburghChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolDivision of Pediatric Respiratory Medicine, Department of Pediatrics, University of California San DiegoChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolAbstract 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.https://doi.org/10.1038/s41525-025-00510-7 |
| spellingShingle | 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 Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS results npj Genomic Medicine |
| title | Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS results |
| title_full | Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS results |
| title_fullStr | Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS results |
| title_full_unstemmed | Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS results |
| title_short | Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS results |
| title_sort | serum microrna expression quantitative trait loci in children with asthma colocalize with asthma related gwas results |
| url | https://doi.org/10.1038/s41525-025-00510-7 |
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