Louise V. Wain
Copy Number Variation of the Beta-Defensin Genes in Europeans: No Supporting Evidence for Association with Lung Function, Chronic Obstructive Pulmonary Disease or Asthma
Wain, Louise V.; Odenthal-Hesse, Linda; Abujaber, Razan; Sayers, Ian; Beardsmore, Caroline; Gaillard, Erol A.; Chappell, Sally; Dogaru, Cristian M.; McKeever, Tricia M.; Guetta-Baranes, Tamar; Kalsheker, Noor; Kuehni, Claudia E.; Hall, Ian P.; Tobin, Martin D.; Hollox, Edward J.
Authors
Linda Odenthal-Hesse
Razan Abujaber
Professor IAN SAYERS ian.sayers@nottingham.ac.uk
Professor of Respiratory Molecular Genetics
Caroline Beardsmore
Erol A. Gaillard
Sally Chappell
Cristian M. Dogaru
TRICIA MCKEEVER tricia.mckeever@nottingham.ac.uk
Professor of Epidemiology and Medical Statistics
Tamar Guetta-Baranes
Noor Kalsheker
Claudia E. Kuehni
IAN HALL IAN.HALL@NOTTINGHAM.AC.UK
Professor of Molecular Medicine
Martin D. Tobin
Edward J. Hollox
Abstract
Lung function measures are heritable, predict mortality and are relevant in diagnosis of chronic obstructive pulmonary disease (COPD). COPD and asthma are diseases of the airways with major public health impacts and each have a heritable component. Genome-wide association studies of SNPs have revealed novel genetic associations with both diseases but only account for a small proportion of the heritability. Complex copy number variation may account for some of the missing heritability. A well-characterised genomic region of complex copy number variation contains beta-defensin genes (DEFB103, DEFB104 and DEFB4), which have a role in the innate immune response. Previous studies have implicated these and related genes as being associated with asthma or COPD. We hypothesised that copy number variation of these genes may play a role in lung function in the general population and in COPD and asthma risk. We undertook copy number typing of this locus in 1149 adult and 689 children using a paralogue ratio test and investigated association with COPD, asthma and lung function. Replication of findings was assessed in a larger independent sample of COPD cases and smoking controls. We found evidence for an association of beta-defensin copy number with COPD in the adult cohort (OR = 1.4, 95%CI:1.02–1.92, P = 0.039) but this finding, and findings from a previous study, were not replicated in a larger follow-up sample(OR = 0.89, 95%CI:0.72–1.07, P = 0.217). No robust evidence of association with asthma in children was observed. We found no evidence for association between beta-defensin copy number and lung function in the general populations. Our findings suggest that previous reports of association of beta-defensin copy number with COPD should be viewed with caution. Suboptimal measurement of copy number can lead to spurious associations. Further beta-defensin copy number measurement in larger sample sizes of COPD cases and children with asthma are needed.
Citation
Wain, L. V., Odenthal-Hesse, L., Abujaber, R., Sayers, I., Beardsmore, C., Gaillard, E. A., …Hollox, E. J. (2014). Copy Number Variation of the Beta-Defensin Genes in Europeans: No Supporting Evidence for Association with Lung Function, Chronic Obstructive Pulmonary Disease or Asthma. PLoS ONE, 9(1), Article e84192. https://doi.org/10.1371/journal.pone.0084192
Journal Article Type | Article |
---|---|
Acceptance Date | Nov 13, 2013 |
Online Publication Date | Jan 3, 2014 |
Publication Date | Jan 3, 2014 |
Deposit Date | Apr 6, 2016 |
Publicly Available Date | Apr 6, 2016 |
Journal | PLoS ONE |
Electronic ISSN | 1932-6203 |
Publisher | Public Library of Science |
Peer Reviewed | Peer Reviewed |
Volume | 9 |
Issue | 1 |
Article Number | e84192 |
DOI | https://doi.org/10.1371/journal.pone.0084192 |
Public URL | https://nottingham-repository.worktribe.com/output/722239 |
Publisher URL | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084192 |
Contract Date | Apr 6, 2016 |
Files
Wain PLoS One 2014.pdf
(595 Kb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
You might also like
Mutation analysis of sporadic early-onset Alzheimer's disease using the NeuroX array
(2016)
Journal Article
Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer’s disease
(2017)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search