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Human Molecular Genetics Advance Access published online on October 27, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh340
© 2004 by Oxford University Press
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Article

Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families

Emmanuelle Bouzigon 1, Marie-Hélène Dizier 2, Christine Krähenbühl 1, Arnaud Lemainque 3, Isabella Annesi-Maesano 4, Christine Betard 3, Jean Bousquet 5, Denis Charpin 6, Frédéric Gormand 7, Michel Guilloud-Bataille 2, Jocelyne Just 8, Nicole Le Moual 4, Jean Maccario 4, Régis Matran 9, Françoise Neukirch 10, Marie-Pierre Oryszczyn 4, Evelyne Paty 11, Isabelle Pin 12, Myriam Rosenberg-Bourgin 1, Daniel Vervloet 13, Francine Kauffmann 4, Mark Lathrop 3, and Florence Demenais 14*

1 INSERM EMI00-06, Evry, France
2 INSERM U535, Villejuif, France
3 Centre National de Génotypage, Evry, France
4 INSERM U472-IFR69, Villejuif, France
5 Clinique des Maladies Respiratoires, INSERM U454, Hôpital Arnaud de Villeneuve, Montpellier, France
6 Service de Pneumologie-Allergologie, Hôpital Nord, Marseille, France
7 Service de Pneumologie, Centre Hospitalier Lyon-Sud, Pierre Benite, France
8 Centre de Diagnostic et Traitement de l'Asthme, Hôpital Trousseau, Paris, France
9 Laboratoire d'Exploration Fonctionnelle, Hôpital Calmette, Lille, France
10 INSERM U408, Paris, France
11 Service de Pneumologie Infantile, Hôpital Necker, Paris, France
12 Service Pneumologie, CHU Michallon, Grenoble, France
13 Service de Pneumo-Allergologie, Hôpital Ste Marguerite, Marseille, France
14 INSERM EMI0006, Tour Evry 2, 523, Place des Terrasses de l'Agora, 91034 Evry Cedex - France

* To whom correspondence should be addressed.
Florence Demenais, E-mail: demenais{at}evry.inserm.fr


  Abstract

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 < P ≤ 0.005). 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, clustering of LODs for %FEV1, BR and SPTQ on another axis, while LODs for IgE and eosinophils appeared to be respectively independent from all other LODs. These results provide new insights in the potential sharing of genetic determinants by asthma-related phenotypes.


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