Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
18442398
TITLE
Meta-analysis of genome-wide linkage studies of asthma and related traits.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Asthma and allergy are complex multifactorial disorders, with both genetic and environmental components determining disease expression. The use of molecular genetics holds great promise for the identification of novel drug targets for the treatment of asthma and allergy. Genome-wide linkage studies have identified a number of potential disease susceptibility loci but replication remains inconsistent. The aim of the current study was to complete a meta-analysis of data from genome-wide linkage studies of asthma and related phenotypes and provide inferences about the consistency of results and to identify novel regions for future gene discovery.
METHODS NlmCategory: METHODS
The rank based genome-scan meta-analysis (GSMA) method was used to combine linkage data for asthma and related traits; bronchial hyper-responsiveness (BHR), allergen positive skin prick test (SPT) and total serum Immunoglobulin E (IgE) from nine Caucasian asthma populations.
RESULTS NlmCategory: RESULTS
Significant evidence for susceptibility loci was identified for quantitative traits including; BHR (989 pedigrees, n = 4,294) 2p12-q22.1, 6p22.3-p21.1 and 11q24.1-qter, allergen SPT (1,093 pedigrees, n = 4,746) 3p22.1-q22.1, 17p12-q24.3 and total IgE (729 pedigrees, n = 3,224) 5q11.2-q14.3 and 6pter-p22.3. Analysis of the asthma phenotype (1,267 pedigrees, n = 5,832) did not identify any region showing genome-wide significance.
CONCLUSION NlmCategory: CONCLUSIONS
This study represents the first linkage meta-analysis to determine the relative contribution of chromosomal regions to the risk of developing asthma and atopy. Several significant results were obtained for quantitative traits but not for asthma confirming the increased phenotype and genetic heterogeneity in asthma. These analyses support the contribution of regions that contain previously identified asthma susceptibility genes and provide the first evidence for susceptibility loci on 5q11.2-q14.3 and 11q24.1-qter.
DATE PUBLISHED
2008
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2007/12/10
accepted 2008/04/28
aheadofprint 2008/04/28
pubmed 2008/04/30 09:00
medline 2008/06/21 09:00
entrez 2008/04/30 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Denham S Denham Samuel S Division of Therapeutics & Molecular Medicine, University Hospital of Nottingham, Nottingham, UK. mzyysnd@exmail.nottingham.ac.uk
Koppelman GH Koppelman Gerard H GH
Blakey J Blakey John J
Wjst M Wjst Matthias M
Ferreira MA Ferreira Manuel A MA
Hall IP Hall Ian P IP
Sayers I Sayers Ian I
INVESTIGATORS
JOURNAL
VOLUME: 9
ISSUE:
TITLE: Respiratory research
ISOABBREVIATION: Respir. Res.
YEAR: 2008
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1465-993X
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Respir Res
COUNTRY: England
ISSNLINKING: 1465-9921
NLMUNIQUEID: 101090633
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
G0400283 Medical Research Council United Kingdom
Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Asthma genetics
Chromosome Mapping genetics
Clinical Trials as Topic statistics & numerical data
Comorbidity statistics & numerical data
Genetic Linkage genetics
Genetic Predisposition to Disease genetics
Genome, Human genetics
Humans genetics
Hypersensitivity genetics
Prevalence genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC2391165 NLM