Pooled Sequencing of Candidate Genes Implicates Rare Variants in the Development of Asthma Following Severe RSV Bronchiolitis in Infancy Article Swipe
Dara G. Torgerson
,
Tusar Giri
,
Todd E. Druley
,
Jie Zheng
,
Scott Huntsman
,
Max A. Seibold
,
Andrew L. Young
,
Toni Schweiger
,
Huiqing Yin‐Declue
,
Geneline Sajol
,
Kenneth B. Schechtman
,
Ryan D. Hernandez
,
Adrienne G. Randolph
,
Leonard B. Bacharier
,
Mario Castro
·
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0142649
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0142649
Severe infection with respiratory syncytial virus (RSV) during infancy is strongly associated with the development of asthma. To identify genetic variation that contributes to asthma following severe RSV bronchiolitis during infancy, we sequenced the coding exons of 131 asthma candidate genes in 182 European and African American children with severe RSV bronchiolitis in infancy using anonymous pools for variant discovery, and then directly genotyped a set of 190 nonsynonymous variants. Association testing was performed for physician-diagnosed asthma before the 7th birthday (asthma) using genotypes from 6,500 individuals from the Exome Sequencing Project (ESP) as controls to gain statistical power. In addition, among patients with severe RSV bronchiolitis during infancy, we examined genetic associations with asthma, active asthma, persistent wheeze, and bronchial hyperreactivity (methacholine PC20) at age 6 years. We identified four rare nonsynonymous variants that were significantly associated with asthma following severe RSV bronchiolitis, including single variants in ADRB2, FLG and NCAM1 in European Americans (p = 4.6x10-4, 1.9x10-13 and 5.0x10-5, respectively), and NOS1 in African Americans (p = 2.3x10-11). One of the variants was a highly functional nonsynonymous variant in ADRB2 (rs1800888), which was also nominally associated with asthma (p = 0.027) and active asthma (p = 0.013) among European Americans with severe RSV bronchiolitis without including the ESP. Our results suggest that rare nonsynonymous variants contribute to the development of asthma following severe RSV bronchiolitis in infancy, notably in ADRB2. Additional studies are required to explore the role of rare variants in the etiology of asthma and asthma-related traits following severe RSV bronchiolitis.
Related Topics
Concepts
Bronchiolitis
Asthma
Nonsynonymous substitution
Medicine
Wheeze
Immunology
Candidate gene
Pediatrics
Biology
Genetics
Gene
Virus
Genome
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pone.0142649
- https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0142649&type=printable
- OA Status
- gold
- Cited By
- 11
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2264704432
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2264704432Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.pone.0142649Digital Object Identifier
- Title
-
Pooled Sequencing of Candidate Genes Implicates Rare Variants in the Development of Asthma Following Severe RSV Bronchiolitis in InfancyWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2015Year of publication
- Publication date
-
2015-11-20Full publication date if available
- Authors
-
Dara G. Torgerson, Tusar Giri, Todd E. Druley, Jie Zheng, Scott Huntsman, Max A. Seibold, Andrew L. Young, Toni Schweiger, Huiqing Yin‐Declue, Geneline Sajol, Kenneth B. Schechtman, Ryan D. Hernandez, Adrienne G. Randolph, Leonard B. Bacharier, Mario CastroList of authors in order
- Landing page
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https://doi.org/10.1371/journal.pone.0142649Publisher landing page
- PDF URL
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0142649&type=printableDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0142649&type=printableDirect OA link when available
- Concepts
-
Bronchiolitis, Asthma, Nonsynonymous substitution, Medicine, Wheeze, Immunology, Candidate gene, Pediatrics, Biology, Genetics, Gene, Virus, GenomeTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
11Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1, 2024: 1, 2021: 2, 2018: 1, 2017: 5Per-year citation counts (last 5 years)
- References (count)
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51Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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