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Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and Lung Function
PURPOSE: Respiratory diseases have a highly multifactorial etiology where different mechanisms contribute to the individual's susceptibility. We conducted a deep characterization of loci associated with asthma and lung function by previous genome-wide association studies (GWAS). METHODS: Sixtee...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean
Academy of Pediatric Allergy and Respiratory Disease
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347000/ https://www.ncbi.nlm.nih.gov/pubmed/32638561 http://dx.doi.org/10.4168/aair.2020.12.5.806 |
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author | Karaca, Mehmet Atceken, Nazente Karaca, Şefayet Civelek, Ersoy Şekerel, Bülent E. Polimanti, Renato |
author_facet | Karaca, Mehmet Atceken, Nazente Karaca, Şefayet Civelek, Ersoy Şekerel, Bülent E. Polimanti, Renato |
author_sort | Karaca, Mehmet |
collection | PubMed |
description | PURPOSE: Respiratory diseases have a highly multifactorial etiology where different mechanisms contribute to the individual's susceptibility. We conducted a deep characterization of loci associated with asthma and lung function by previous genome-wide association studies (GWAS). METHODS: Sixteen variants were selected from previous GWAS of childhood/adult asthma and pulmonary function tests. We conducted a phenome-wide association study of these loci in 4,083 traits assessed in the UK Biobank (n = 361,194 participants). Data from the Genotype-Tissue Expression (GTEx) project were used to conduct a transcriptomic analysis with respect to tissues relevant for asthma pathogenesis. A pediatric cohort assessed with the International Study of Asthma and Allergies in Children (ISAAC) Phase II tools was used to further explore the association of these variants with 116 traits related to asthma comorbidities. RESULTS: Our phenome-wide association studies (PheWAS) identified 206 phenotypic associations with respect to the 16 variants identified. In addition to the replication of the phenotypes tested in the discovery GWAS, we observed novel associations related to blood levels of immune cells (eosinophils, neutrophils, monocytes, and lymphocytes) for the asthma-related variants. Conversely, the lung-function variants were associated with phenotypes related to body fat mass. In the ISAAC-assessed cohort, we observed that risk alleles associated with increased fat mass can exacerbate allergic reactions in individuals affected by allergic respiratory diseases. The GTEx-based analysis showed that the variants tested affect the transcriptomic regulation of multiple surrounding genes across several tissues. CONCLUSIONS: This study generated novel data regarding the genetics of respiratory diseases and their comorbidities, providing a deep characterization of loci associated with asthma and lung function. |
format | Online Article Text |
id | pubmed-7347000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean
Academy of Pediatric Allergy and Respiratory Disease |
record_format | MEDLINE/PubMed |
spelling | pubmed-73470002020-09-01 Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and Lung Function Karaca, Mehmet Atceken, Nazente Karaca, Şefayet Civelek, Ersoy Şekerel, Bülent E. Polimanti, Renato Allergy Asthma Immunol Res Original Article PURPOSE: Respiratory diseases have a highly multifactorial etiology where different mechanisms contribute to the individual's susceptibility. We conducted a deep characterization of loci associated with asthma and lung function by previous genome-wide association studies (GWAS). METHODS: Sixteen variants were selected from previous GWAS of childhood/adult asthma and pulmonary function tests. We conducted a phenome-wide association study of these loci in 4,083 traits assessed in the UK Biobank (n = 361,194 participants). Data from the Genotype-Tissue Expression (GTEx) project were used to conduct a transcriptomic analysis with respect to tissues relevant for asthma pathogenesis. A pediatric cohort assessed with the International Study of Asthma and Allergies in Children (ISAAC) Phase II tools was used to further explore the association of these variants with 116 traits related to asthma comorbidities. RESULTS: Our phenome-wide association studies (PheWAS) identified 206 phenotypic associations with respect to the 16 variants identified. In addition to the replication of the phenotypes tested in the discovery GWAS, we observed novel associations related to blood levels of immune cells (eosinophils, neutrophils, monocytes, and lymphocytes) for the asthma-related variants. Conversely, the lung-function variants were associated with phenotypes related to body fat mass. In the ISAAC-assessed cohort, we observed that risk alleles associated with increased fat mass can exacerbate allergic reactions in individuals affected by allergic respiratory diseases. The GTEx-based analysis showed that the variants tested affect the transcriptomic regulation of multiple surrounding genes across several tissues. CONCLUSIONS: This study generated novel data regarding the genetics of respiratory diseases and their comorbidities, providing a deep characterization of loci associated with asthma and lung function. The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease 2020-05-11 /pmc/articles/PMC7347000/ /pubmed/32638561 http://dx.doi.org/10.4168/aair.2020.12.5.806 Text en Copyright © 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Karaca, Mehmet Atceken, Nazente Karaca, Şefayet Civelek, Ersoy Şekerel, Bülent E. Polimanti, Renato Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and Lung Function |
title | Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and
Lung Function |
title_full | Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and
Lung Function |
title_fullStr | Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and
Lung Function |
title_full_unstemmed | Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and
Lung Function |
title_short | Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and
Lung Function |
title_sort | phenotypic and molecular characterization of risk loci associated with asthma and
lung function |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347000/ https://www.ncbi.nlm.nih.gov/pubmed/32638561 http://dx.doi.org/10.4168/aair.2020.12.5.806 |
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