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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0084192&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850125355555225600 |
|---|---|
| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-82f2d49534d3480ea8d9902b1ed39aec |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-82f2d49534d3480ea8d9902b1ed39aec2025-08-20T02:34:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8419210.1371/journal.pone.0084192Copy number variation of the beta-defensin genes in europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma.Louise V WainLinda Odenthal-HesseRazan AbujaberIan SayersCaroline BeardsmoreErol A GaillardSally ChappellCristian M DogaruTricia McKeeverTamar Guetta-BaranesNoor KalshekerClaudia E KuehniIan P HallMartin D TobinEdward J HolloxLung 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0084192&type=printable |
| spellingShingle | 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. PLoS ONE |
| 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://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0084192&type=printable |
| work_keys_str_mv | AT louisevwain copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT lindaodenthalhesse copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT razanabujaber copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT iansayers copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT carolinebeardsmore copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT erolagaillard copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT sallychappell copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT cristianmdogaru copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT triciamckeever copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT tamarguettabaranes copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT noorkalsheker copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT claudiaekuehni copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT ianphall copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT martindtobin copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma AT edwardjhollox copynumbervariationofthebetadefensingenesineuropeansnosupportingevidenceforassociationwithlungfunctionchronicobstructivepulmonarydiseaseorasthma |