Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy.
Asthma is caused by a heterogeneous combination of environmental and genetic factors. In the context of GA2LEN (Global Allergy and Asthma European Network), we carried out meta-analyses of almost all genome-wide linkage screens conducted to date in 20 independent populations from different ethnic origins (>or=3024 families with >or=10 027 subjects) for asthma, atopic asthma, bronchial hyper-responsiveness and five atopy-related traits (total immunoglobulin E level, positive skin test response (SPT) to at least one allergen or to House Dust Mite, quantitative score of SPT (SPTQ) and eosinophils (EOS)). We used the genome scan meta-analysis method to assess evidence for linkage within bins of traditionally 30-cM width, and explored the manner in which these results were affected by bin definition. Meta-analyses were conducted in all studies and repeated in families of European ancestry. Genome-wide evidence for linkage was detected for asthma in two regions (2p21-p14 and 6p21) in European families ascertained through two asthmatic sibs. With regard to atopy phenotypes, four regions reached genome-wide significance: 3p25.3-q24 in all families for SPT and three other regions in European families (2q32-q34 for EOS, 5q23-q33 for SPTQ and 17q12-q24 for SPT). Tests of heterogeneity showed consistent evidence of linkage of SPTQ to 3p11-3q21, whereas between-study heterogeneity was detected for asthma in 2p22-p13 and 6p21, and for atopic asthma in 1q23-q25. This large-scale meta-analysis provides an important resource of information that can be used to prioritize further fine-mapping studies and also be integrated with genome-wide association studies to increase power and better interpret the outcomes of these studies.
Bouzigon
Emmanuelle
E
INSERM, U946, Paris, France. emmanuelle.bouzigon@inserm.fr
Forabosco
Paola
P
Koppelman
Gerard H
GH
Cookson
William O C M
WO
Dizier
Marie-Hélène
MH
Duffy
David L
DL
Evans
David M
DM
Ferreira
Manuel A R
MA
Kere
Juha
J
Laitinen
Tarja
T
Malerba
Giovanni
G
Meyers
Deborah A
DA
Moffatt
Miriam
M
Martin
Nicholas G
NG
Ng
Mandy Y
MY
Pignatti
Pier Franco
PF
Wjst
Mathias
M
Kauffmann
Francine
F
Demenais
Florence
F
Lewis
Cathryn M
CM
D001249:Asthma / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D001772:Blood Cell Count; D002874:Chromosome Mapping; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D007073:Immunoglobulin E / Q000032:analysis / Q000097:blood; D010641:Phenotype
D007073:Immunoglobulin E