Human Molecular Genetics Advance Access originally published online on October 27, 2004
Human Molecular Genetics 2004 13(24):3103-3113; doi:10.1093/hmg/ddh340
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Human Molecular Genetics, Vol. 13, No. 24 © Oxford University Press 2004; all rights reserved
Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families
1INSERM EMI0006, Evry, France, 2INSERM U535, Villejuif, France, 3Centre National de Génotypage, Evry, France, 4INSERM U472-IFR69, Villejuif, France, 5Clinique des Maladies Respiratoires, INSERM U454, Hôpital Arnaud de Villeneuve, Montpellier, France, 6Service de Pneumologie-Allergologie, Hôpital Nord, Marseille, France, 7Service de Pneumologie, Centre Hospitalier Lyon-Sud, Pierre Benite, France, 8Centre de Diagnostic et Traitement de l'Asthme, Hôpital Trousseau, Paris, France, 9Laboratoire d'Exploration Fonctionnelle, Hôpital Calmette, Lille, France, 10INSERM U408, Paris, France, 11Service de Pneumologie Infantile, Hôpital Necker, Paris, France, 12Service Pneumologie, CHU Michallon, Grenoble, France and 13Service de Pneumo-Allergologie, Hôpital Ste Marguerite, Marseille, France
Received July 28, 2004; Accepted October 19, 2004
A genome-wide scan for asthma phenotypes was conducted in the whole sample of 295 EGEA families selected through at least one asthmatic subject. In addition to asthma, seven phenotypes involved in the main asthma physiopathological pathways were considered: SPT (positive skin prick test response to at least one of 11 allergens), SPTQ score being the number of positive skin test responses to 11 allergens, Phadiatop® (positive specific IgE response to a mixture of allergens), total IgE levels, eosinophils, bronchial responsiveness (BR) to methacholine challenge and %predicted FEV1. Four regions showed evidence for linkage (P
0.001): 6q14 for %FEV1, 12p13 for IgE, 17q22–q24 for SPT and 21q21 for both SPTQ and %FEV1. Nine other regions indicated smaller linkage signals (0.001<P0.005). While most of these regions have been reported by previous asthma and lung function screens, 6q14 appears to be a new region potentially linked to %FEV1. To determine which of these various asthma phenotypes are more likely to share common genetic determinants, a principal component analysis was applied to the genome-wide LOD scores. This analysis revealed clustering of LODs for asthma, SPT and Phadiatop® on one axis and clustering of LODs for %FEV1, BR and SPTQ on the other, while LODs for IgE and eosinophils appeared to be independent from all other LODs. These results provide new insights into the potential sharing of genetic determinants by asthma-related phenotypes.
* To whom correspondence should be addressed at: INSERM EMI0006, Tour Evry 2, 523, Place des Terrasses de l'Agora, 91034 Evry Cedex France. Tel: +33 160873820; Fax: +33 160873848; Email: demenais{at}evry.inserm.fr
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