Phenotypic and genetic heterogeneity in a genome-wide linkage study of asthma families

被引：32
作者：
Altmüller J. [1 ,2 ]
Seidel C. [1 ,10 ]
Lee Y.-A. [2 ]
Loesgen S. [3 ]
Bulle D. [4 ]
Friedrichs F. [5 ]
Jellouschek H. [6 ]
Kelber J. [7 ]
Keller A. [8 ]
Schuster A. [9 ]
Silbermann M. [10 ]
Wahlen W. [11 ]
Wolff P. [12 ]
Schlenvoigt G. [13 ]
Rüschendorf F. [2 ]
Nürnberg P. [2 ]
Wjst M. [1 ]
机构：
[1] GSF Institute of Epidemiology, GSF Natl. Res. Ctr. Environ./Health, Neuherberg
[2] MDC Gene Mapping Center, Max-Delbruck Ctr. Molecular Medicine, Berlin
[3] LoesGen, Oberbözberg
[4] Praxis für Kinderheilkunde, Ravensburg
[5] FF and K. Zima, Praxis für Kinderheilkunde, Aachen-Laurensberg
[6] HJ and M. Barker, Klin. Kinderheilkunde RWTH Aachen, Aachen
[7] JK and W. Leopold, Klinik fur Kinder und Jugendliche, Univ. Klinikums Carl Gustav Carl, Dresden
[8] AK and W. Rebien, Praxis für Kinderheilkunde, Hamburg
[9] Universitätskinderklinik, Düsseldorf
[10] Praxis für Kinderheilkunde, Berlin
[11] Praxis für Kinderheilkunde, Homburg
[12] Praxis für Kinderheilkunde, Pfullendorf
[13] Institut für Immunologie, Universität Jena, Jena
来源：
BMC Pulmonary Medicine | / 5卷 / 1期
关键词：
Asthma; Severe Asthma; Skin Prick Test; House Dust Mite; Suggestive Linkage;
D O I：
10.1186/1471-2466-5-1
中图分类号：
学科分类号：
摘要：
Background. Asthma is a complex genetic disease with more than 20 genome-wide scans conducted so far. Regions on almost every chromosome have been linked to asthma and several genes have been associated. However, most of these associations are weak and are still awaiting replication. Methods. In this study, we conducted a second-stage genome-wide scan with 408 microsatellite markers on 201 asthma-affected sib pair families and defined clinical subgroups to identify phenotype-genotype relations. Results. The lowest P value for asthma in the total sample was 0.003 on chromosome 11, while several of the clinical subsets reached lower significance levels than in the overall sample. Suggestive evidence for linkage (p=0.0007) was found for total IgE on chromosomes 1, 7 and again on chromosome 11, as well as for HDM asthma on chromosome 12. Weaker linkage signals could be found on chromosomes 4 and 5 for early onset and HDM, and, newly described, on chromosome 2 for severe asthma and on chromosome 9 for hay fever. Conclusions. This phenotypic dissection underlines the importance of detailed clinical characterisations and the extreme genetic heterogeneity of asthma. © 2005 Altmuller et al., licensee BioMed Central Ltd.
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页数：10
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