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Genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma
While genome-wide association studies have identified genes involved in differential treatment responses to inhaled corticosteroids (ICS) in asthma, few studies have evaluated the potential effects of age in this context. A significant proportion of asthmatics experience exacerbations (hospitalizati...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051058/ https://www.ncbi.nlm.nih.gov/pubmed/32119686 http://dx.doi.org/10.1371/journal.pone.0229241 |
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author | Dahlin, Amber Sordillo, Joanne E. McGeachie, Michael Kelly, Rachel S. Tantisira, Kelan G. Lutz, Sharon M. Lasky-Su, Jessica Wu, Ann Chen |
author_facet | Dahlin, Amber Sordillo, Joanne E. McGeachie, Michael Kelly, Rachel S. Tantisira, Kelan G. Lutz, Sharon M. Lasky-Su, Jessica Wu, Ann Chen |
author_sort | Dahlin, Amber |
collection | PubMed |
description | While genome-wide association studies have identified genes involved in differential treatment responses to inhaled corticosteroids (ICS) in asthma, few studies have evaluated the potential effects of age in this context. A significant proportion of asthmatics experience exacerbations (hospitalizations and emergency department visits) during ICS treatment. We evaluated the interaction of genetic variation and age on ICS response (measured by the occurrence of exacerbations) through a genome-wide interaction study (GWIS) of 1,321 adult and child asthmatic patients of European ancestry. We identified 107 genome-wide suggestive (P<10(−05)) age-by-genotype interactions, two of which also met genome-wide significance (P<5x10(-08)) (rs34631960 [OR 2.3±1.6–3.3] in thrombospondin type 1 domain-containing protein 4 (THSD4) and rs2328386 [OR 0.5±0.3–0.7] in human immunodeficiency virus type I enhancer binding protein 2 (HIVEP2)) by joint analysis of GWIS results from discovery and replication populations. In addition to THSD4 and HIVEP2, age-by-genotype interactions also prioritized genes previously identified as asthma candidate genes, including DPP10, HDAC9, TBXAS1, FBXL7, and GSDMB/ORMDL3, as pharmacogenomic loci as well. This study is the first to link these genes to a pharmacogenetic trait for asthma. |
format | Online Article Text |
id | pubmed-7051058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70510582020-03-12 Genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma Dahlin, Amber Sordillo, Joanne E. McGeachie, Michael Kelly, Rachel S. Tantisira, Kelan G. Lutz, Sharon M. Lasky-Su, Jessica Wu, Ann Chen PLoS One Research Article While genome-wide association studies have identified genes involved in differential treatment responses to inhaled corticosteroids (ICS) in asthma, few studies have evaluated the potential effects of age in this context. A significant proportion of asthmatics experience exacerbations (hospitalizations and emergency department visits) during ICS treatment. We evaluated the interaction of genetic variation and age on ICS response (measured by the occurrence of exacerbations) through a genome-wide interaction study (GWIS) of 1,321 adult and child asthmatic patients of European ancestry. We identified 107 genome-wide suggestive (P<10(−05)) age-by-genotype interactions, two of which also met genome-wide significance (P<5x10(-08)) (rs34631960 [OR 2.3±1.6–3.3] in thrombospondin type 1 domain-containing protein 4 (THSD4) and rs2328386 [OR 0.5±0.3–0.7] in human immunodeficiency virus type I enhancer binding protein 2 (HIVEP2)) by joint analysis of GWIS results from discovery and replication populations. In addition to THSD4 and HIVEP2, age-by-genotype interactions also prioritized genes previously identified as asthma candidate genes, including DPP10, HDAC9, TBXAS1, FBXL7, and GSDMB/ORMDL3, as pharmacogenomic loci as well. This study is the first to link these genes to a pharmacogenetic trait for asthma. Public Library of Science 2020-03-02 /pmc/articles/PMC7051058/ /pubmed/32119686 http://dx.doi.org/10.1371/journal.pone.0229241 Text en © 2020 Dahlin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Dahlin, Amber Sordillo, Joanne E. McGeachie, Michael Kelly, Rachel S. Tantisira, Kelan G. Lutz, Sharon M. Lasky-Su, Jessica Wu, Ann Chen Genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma |
title | Genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma |
title_full | Genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma |
title_fullStr | Genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma |
title_full_unstemmed | Genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma |
title_short | Genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma |
title_sort | genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051058/ https://www.ncbi.nlm.nih.gov/pubmed/32119686 http://dx.doi.org/10.1371/journal.pone.0229241 |
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