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Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy.
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. et al
European Journal of Human Genetics 18, 6 (2010) 700-6 - http://www.hal.inserm.fr/inserm-00748654
Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy.
Emmanuelle Bouzigon () 1, 2, Paola Forabosco3, 4, Gerard Koppelman5, William Cookson6, Marie-Hélène Dizier7, David Duffy8, David Evans9, Manuel Ferreira8, Juha Kere10, Tarja Laitinen11, Giovanni Malerba12, Deborah Meyers13, Miriam Moffatt6, Nicholas Martin8, Mandy Ng14, Pier Franco Pignatti12, Mathias Wjst15, 16, Francine Kauffmann17, Florence Demenais1, 2, Cathryn Lewis3, 14
1 :  CEPH - Centre d'Etude du Polymorphisme Humain
Institut Universitaire d'Hématologie – Fondation Jean Dausset – Université Paris VII - Paris Diderot
27, rue Juliette Dodu, 75010 Paris
2 :  Variabilité Génétique et Maladies Humaines
Université Paris VII - Paris Diderot – INSERM : U946
Igm fondation Jean Dausset ceph 27 rue Juliette Dodu 4eme etage 75010 paris
3 :  Department of Medical and Molecular Genetics
King's College London
4 :  Istituto di Genetica delle Popolazioni-CNR
5 :  Department of Pulmonary Medicine and Tuberculosis
University of Groningen
University Medical Center Groninge, Speckbacherstr. 31-33, A-6020 Innsbruck
6 :  NHLI - National Heart and Lung Institute
Imperial College London
South Kensington Campus, London SW7 2AZ
7 :  Génétique épidémiologique et structures des populations humaines
INSERM : U535 – IFR69 – Université Paris XI - Paris Sud
Hopital Paul Brousse 94817 VILLEJUIF CEDEX
8 :  Queensland Institute of Medical Research
Queensland Institute of Medical Research – Royal Brisbane Hospital
9 :  Department of Social Medicine
University of Bristol
Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK
10 :  Department of Biosciences and Nutrition
Karolinska Institutet
11 :  Departments of Pulmonary Medicine and Medical Genetics
University of Helsinki
12 :  Section of Biology & Genetics
University of Verona
Department of Life and Reproduction Sciences, Verona
13 :  Center for Human Genomics
Wake Forest University
Winston Salem NC
14 :  MRC SGDP Centre
King's College London
Institute of Psychiatry, London
15 :  Institute of Experimental Pneumology
Helmholtz Zentrum München
German Research Center for Environmental Health, Neuherberg
16 :  EURAC research
Institute of Genetic Medicine
17 :  Recherche en épidémiologie et biostatistique
INSERM : IFR69 – Université Paris XI - Paris Sud
16, Avenue Paul Vaillant-Couturier 94807 VILLEJUIF CEDEX
Asthma and atopy genome linkage scan meta-analyses
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.
Sciences du Vivant/Santé publique et épidémiologie

Articles dans des revues avec comité de lecture
European Journal of Human Genetics (Eur J Hum Genet)
Publisher Nature Publishing Group: Open Access Hybrid Model Option B
ISSN 1018-4813 (eISSN : 1476-5438)

Asthma – Blood Cell Count – Chromosome Mapping – Eosinophils – Genetic Heterogeneity – Genetic Linkage – Genome-Wide Association Study – Humans – Hypersensitivity – Immediate – Immunoglobulin E – Phenotype
This study was supported by the European Commission as part of the GA2LEN project, Global Allergy and Asthma European Network (contract no. FOOD-CT-2004-506378) and GABRIEL, a multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community (contract no. 01896 under the Integrated Programme LSH-2004-1.2.5-1
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