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.
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.
authors.affiliation: Department of Health Sciences, University of Leicester, Leicester, United Kingdom.
authors.forename: Louise V
authors.initials: LV
authors.lastname: Wain
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Linda
authors.initials: L
authors.lastname: Odenthal-Hesse
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Razan
authors.initials: R
authors.lastname: Abujaber
authors.affiliation: Division of Respiratory Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Sayers
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom ; Institute for Lung Health, National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Beardsmore
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom ; Institute for Lung Health, National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Erol A
authors.initials: EA
authors.lastname: Gaillard
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Chappell
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Cristian M
authors.initials: CM
authors.lastname: Dogaru
authors.affiliation: School of Community Health Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Tricia
authors.initials: T
authors.lastname: McKeever
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Tamar
authors.initials: T
authors.lastname: Guetta-Baranes
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Noor
authors.initials: N
authors.lastname: Kalsheker
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Kuehni
authors.affiliation: Division of Respiratory Medicine, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hall
authors.affiliation: Department of Health Sciences, University of Leicester, Leicester, United Kingdom ; Department of Genetics, University of Leicester, Leicester, United Kingdom ; Institute for Lung Health, National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Tobin
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hollox
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology; D044465:White People / Q000235:genetics*; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D023083:beta-Defensins