Copy number variation of the beta-defensin genes in Europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma
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 reveal...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
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Public Library of Science
2014
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| Online Access: | https://eprints.nottingham.ac.uk/32656/ |
| _version_ | 1848794459871903744 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Ahuja, Sunil K. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:16:32Z |
| format | Article |
| id | nottingham-32656 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:16:32Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-326562020-05-04T16:42:13Z https://eprints.nottingham.ac.uk/32656/ 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. 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. Public Library of Science 2014-01-03 Article PeerReviewed 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. and Hollox, Edward 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). e84192/1-e84192/8. ISSN 1932-6203 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084192 doi:10.1371/journal.pone.0084192 doi:10.1371/journal.pone.0084192 |
| spellingShingle | 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. Copy number variation of the beta-defensin genes in Europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma |
| title | Copy number variation of the beta-defensin genes in Europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma |
| title_full | Copy number variation of the beta-defensin genes in Europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma |
| title_fullStr | Copy number variation of the beta-defensin genes in Europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma |
| title_full_unstemmed | Copy number variation of the beta-defensin genes in Europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma |
| title_short | Copy number variation of the beta-defensin genes in Europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma |
| title_sort | copy number variation of the beta-defensin genes in europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma |
| url | https://eprints.nottingham.ac.uk/32656/ https://eprints.nottingham.ac.uk/32656/ https://eprints.nottingham.ac.uk/32656/ |