Scores of asthma and asthma severity reveal new regions of linkage in EGEA families

¹ INSERM, U794, Evry, France; and Université d'Evry, Evry, France
² INSERM, U823, Grenoble, France
³ INSERM, U535, Villejuif, France; and Univ Paris-Sud, IFR69, Villejuif, France
⁴ Centre National de Génotypage, Evry, France
⁵ INSERM, U884, Grenoble, France; and INSERM, U780, Villejuif, France
⁶ Univ Paris-Sud, IFR69, Villejuif, France; and INSERM, U780, Villejuif, France
⁷ INSERM, U794, Evry, France
⁸ Université d'Evry, Evry, France

^* To whom correspondence should be addressed. E-mail: bouzigon{at}evry.inserm.fr.

	Abstract

There is a debate on how asthma should be defined to progress in the understanding of underlying mechanisms. Our goal was to build quantitative scores of asthma and asthma severity and to assess whether refining disease phenotypes can facilitate the identification of chromosomal regions harboring susceptibility genes.

A genome-wide linkage scan was conducted in 110 families with 2 asthmatic sibs (n=508) from the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA). Phenotypes studied were an asthma severity score assessed among asthmatics by combining clinical data and treatment, forced expiratory volume in 1 second (FEV₁) and an asthma score including both asthmatics and non-asthmatics and representing the whole disease spectrum.

Our analysis showed genome-wide suggestive evidence for linkage of asthma score to 18p11 (p=0.0004), a novel region undetected by our previous screen of dichotomous asthma. There was potential linkage of 2p23 to asthma severity score (p=0.002) and of three regions to FEV₁: 1p36 (p=0.004), 2q36 (p=0.003) and 6q14 (p=0.003). Moreover, FEV₁ appeared to have no genetic determinant in common with asthma severity and asthma scores.

Asthma and asthma severity quantitative scores revealed new regions of linkage and thus provides support for considering these phenotypes in future genetic studies.

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