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...

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Autores principales:	Louise V Wain, Linda Odenthal-Hesse, Razan Abujaber, Ian Sayers, Caroline Beardsmore, Erol A Gaillard, Sally Chappell, Cristian M Dogaru, Tricia McKeever, Tamar Guetta-Baranes, Noor Kalsheker, Claudia E Kuehni, Ian P Hall, Martin D Tobin, Edward J Hollox
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/82f2d49534d3480ea8d9902b1ed39aec
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spelling	oai:doaj.org-article:82f2d49534d3480ea8d9902b1ed39aec2021-11-18T08:38:59ZCopy number variation of the beta-defensin genes in europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma.1932-620310.1371/journal.pone.0084192https://doaj.org/article/82f2d49534d3480ea8d9902b1ed39aec2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24404154/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Lung 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.Louise V WainLinda Odenthal-HesseRazan AbujaberIan SayersCaroline BeardsmoreErol A GaillardSally ChappellCristian M DogaruTricia McKeeverTamar Guetta-BaranesNoor KalshekerClaudia E KuehniIan P HallMartin D TobinEdward J HolloxPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e84192 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Louise V Wain Linda Odenthal-Hesse Razan Abujaber Ian Sayers Caroline Beardsmore Erol A Gaillard Sally Chappell Cristian M Dogaru Tricia McKeever Tamar Guetta-Baranes Noor Kalsheker Claudia E Kuehni Ian P Hall Martin D Tobin Edward J Hollox Copy number variation of the beta-defensin genes in europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma.
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.
format	article
author	Louise V Wain Linda Odenthal-Hesse Razan Abujaber Ian Sayers Caroline Beardsmore Erol A Gaillard Sally Chappell Cristian M Dogaru Tricia McKeever Tamar Guetta-Baranes Noor Kalsheker Claudia E Kuehni Ian P Hall Martin D Tobin Edward J Hollox
author_facet	Louise V Wain Linda Odenthal-Hesse Razan Abujaber Ian Sayers Caroline Beardsmore Erol A Gaillard Sally Chappell Cristian M Dogaru Tricia McKeever Tamar Guetta-Baranes Noor Kalsheker Claudia E Kuehni Ian P Hall Martin D Tobin Edward J Hollox
author_sort	Louise V Wain
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_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_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_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.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/82f2d49534d3480ea8d9902b1ed39aec
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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.

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