Research Repository

See what's under the surface

Copy number variation of the beta-defensin genes in Europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma

Ahuja, Sunil K.; 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

Sunil K. Ahuja

Louise V. Wain

Linda Odenthal-Hesse

Razan Abujaber

Ian Sayers

Caroline Beardsmore

Erol A. Gaillard

Sally Chappell

Cristian M. Dogaru

Tricia M. McKeever

Tamar Guetta-Baranes

Noor Kalsheker

Claudia E. Kuehni

Ian P. Hall

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.

Journal Article Type Article
Publication Date Jan 3, 2014
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 1
Article Number e84192
Institution Citation Ahuja, S. K., Wain, L. V., Odenthal-Hesse, L., Abujaber, R., Sayers, I., Beardsmore, C., …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), doi:10.1371/journal.pone.0084192
DOI https://doi.org/10.1371/journal.pone.0084192
Publisher URL http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084192
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

Files

Wain PLoS One 2014.pdf (595 Kb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0




Downloadable Citations