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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.

Copy Number Variation of the Beta-Defensin Genes in Europeans: No Supporting Evidence for Association with Lung Function, Chronic Obstructive Pulmonary Disease or Asthma Thumbnail


Authors

Louise V. Wain

Linda Odenthal-Hesse

Razan Abujaber

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

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