Peripheral blood miRNAs are associated with airflow below threshold in children with asthma

Abstract Background MicroRNAs (miRNAs) are crucial post-transcriptional regulators involved in inflammatory diseases, such as asthma. Poor lung function and airflow issues in childhood are linked to the development of chronic obstructive pulmonary disease (COPD) in adulthood. Methods We analyzed sma...

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Main Authors: Anshul Tiwari, Brian D. Hobbs, Rinku Sharma, Jiang Li, Alvin T. Kho, Sami Amr, Juan C. Celedón, Scott T. Weiss, Craig P. Hersh, Kelan G. Tantisira, Michael J. McGeachie
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Language:English
Published: BMC 2025-01-01
Series:Respiratory Research
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Online Access:https://doi.org/10.1186/s12931-025-03116-w
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author Anshul Tiwari
Brian D. Hobbs
Rinku Sharma
Jiang Li
Alvin T. Kho
Sami Amr
Juan C. Celedón
Scott T. Weiss
Craig P. Hersh
Kelan G. Tantisira
Michael J. McGeachie
author_facet Anshul Tiwari
Brian D. Hobbs
Rinku Sharma
Jiang Li
Alvin T. Kho
Sami Amr
Juan C. Celedón
Scott T. Weiss
Craig P. Hersh
Kelan G. Tantisira
Michael J. McGeachie
author_sort Anshul Tiwari
collection DOAJ
description Abstract Background MicroRNAs (miRNAs) are crucial post-transcriptional regulators involved in inflammatory diseases, such as asthma. Poor lung function and airflow issues in childhood are linked to the development of chronic obstructive pulmonary disease (COPD) in adulthood. Methods We analyzed small RNA-Seq data from 365 peripheral whole blood samples from the Genetics of Asthma in Costa Rica Study (GACRS) for association with airflow levels measured by FEV1/FVC. Differentially expressed (DE) miRNAs were identified using DESeq2 in R, adjusting for covariates and applying a 10% false discovery rate (FDR). The analysis included 361 samples and 649 miRNAs. The two DE miRNAs were further tested for association with airflow obstruction in a study of adult former smokers with and without COPD. Results We found 1 upregulated and 1 downregulated miRNA in participants with airflow below the threshold compared to those above it. In the adult study, the same miRNAs were upregulated and downregulated in individuals with FEV1/FVC < 0.7 versus those with FEV1/FVC > 0.7, showing suggestive statistical evidence. The target genes of these miRNAs were enriched for PI3K-Akt, Hippo, WNT, MAPK, and focal adhesion pathways. Conclusions Two differentially expressed miRNAs were associated with airflow levels in children with asthma and airflow obstruction in adults with COPD. This suggests that shared genetic regulatory systems may influence childhood airflow and contribute to adulthood airflow obstruction.
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spelling doaj-art-922aa9320edf435798fec4729e5f06382025-01-26T12:48:57ZengBMCRespiratory Research1465-993X2025-01-0126111310.1186/s12931-025-03116-wPeripheral blood miRNAs are associated with airflow below threshold in children with asthmaAnshul Tiwari0Brian D. Hobbs1Rinku Sharma2Jiang Li3Alvin T. Kho4Sami Amr5Juan C. Celedón6Scott T. Weiss7Craig P. Hersh8Kelan G. Tantisira9Michael J. McGeachie10Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolTranslational Genomics Core, Mass General Brigham Personalized MedicineDivision of Pediatric Pulmonary Medicine, UPMC Children’s Hospital of Pittsburgh, University of PittsburghChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDivision of Pediatric Respiratory Medicine, University of California San Diego and Rady Children’s HospitalChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolAbstract Background MicroRNAs (miRNAs) are crucial post-transcriptional regulators involved in inflammatory diseases, such as asthma. Poor lung function and airflow issues in childhood are linked to the development of chronic obstructive pulmonary disease (COPD) in adulthood. Methods We analyzed small RNA-Seq data from 365 peripheral whole blood samples from the Genetics of Asthma in Costa Rica Study (GACRS) for association with airflow levels measured by FEV1/FVC. Differentially expressed (DE) miRNAs were identified using DESeq2 in R, adjusting for covariates and applying a 10% false discovery rate (FDR). The analysis included 361 samples and 649 miRNAs. The two DE miRNAs were further tested for association with airflow obstruction in a study of adult former smokers with and without COPD. Results We found 1 upregulated and 1 downregulated miRNA in participants with airflow below the threshold compared to those above it. In the adult study, the same miRNAs were upregulated and downregulated in individuals with FEV1/FVC < 0.7 versus those with FEV1/FVC > 0.7, showing suggestive statistical evidence. The target genes of these miRNAs were enriched for PI3K-Akt, Hippo, WNT, MAPK, and focal adhesion pathways. Conclusions Two differentially expressed miRNAs were associated with airflow levels in children with asthma and airflow obstruction in adults with COPD. This suggests that shared genetic regulatory systems may influence childhood airflow and contribute to adulthood airflow obstruction.https://doi.org/10.1186/s12931-025-03116-wmiRNAsAsthmaAirflow obstructionCOPDDifferential expressionFEV1/FVC ratio
spellingShingle Anshul Tiwari
Brian D. Hobbs
Rinku Sharma
Jiang Li
Alvin T. Kho
Sami Amr
Juan C. Celedón
Scott T. Weiss
Craig P. Hersh
Kelan G. Tantisira
Michael J. McGeachie
Peripheral blood miRNAs are associated with airflow below threshold in children with asthma
Respiratory Research
miRNAs
Asthma
Airflow obstruction
COPD
Differential expression
FEV1/FVC ratio
title Peripheral blood miRNAs are associated with airflow below threshold in children with asthma
title_full Peripheral blood miRNAs are associated with airflow below threshold in children with asthma
title_fullStr Peripheral blood miRNAs are associated with airflow below threshold in children with asthma
title_full_unstemmed Peripheral blood miRNAs are associated with airflow below threshold in children with asthma
title_short Peripheral blood miRNAs are associated with airflow below threshold in children with asthma
title_sort peripheral blood mirnas are associated with airflow below threshold in children with asthma
topic miRNAs
Asthma
Airflow obstruction
COPD
Differential expression
FEV1/FVC ratio
url https://doi.org/10.1186/s12931-025-03116-w
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