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Bouzigon, E.* ; Forabosco, P.* ; Koppelman, G.H.* ; Cookson, W.O.C.M.* ; Dizier, M.H.* ; Duffy, D.L.* ; Evans, D.M.* ; Ferreira, M.A.R.* ; Kere, J.* ; Laitinen, T.* ; Malerba, G.* ; Meyers, D.A.* ; Moffatt, M.* ; Martin, N.G.* ; Ng, M.Y.* ; Pignatti, P.F.* ; Wjst, M. ; Kauffmann, F.* ; Demenais, F.* ; Lewis, C.M.*

Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy.

Eur. J. Hum. Genet. 18, 700-706 (2010)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Asthma; Atopy; Meta-analysis; Linkage scan
ISSN (print) / ISBN 1018-4813
e-ISSN 1476-5438
Quellenangaben Band: 18, Heft: 6, Seiten: 700-706 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Begutachtungsstatus Peer reviewed