Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy. - Archive ouverte HAL Access content directly
Journal Articles European Journal of Human Genetics Year : 2010

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

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Mandy Y. Ng
  • Function : Author

Abstract

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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Dates and versions

inserm-00748654 , version 1 (05-11-2012)

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Emmanuelle Bouzigon, Paola Forabosco, Gerard H. Koppelman, William O. C. M. Cookson, Marie-Hélène Dizier, et al.. Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy.: Asthma and atopy genome linkage scan meta-analyses. European Journal of Human Genetics, 2010, 18 (6), pp.700-6. ⟨10.1038/ejhg.2009.224⟩. ⟨inserm-00748654⟩
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