1. ¹INSERM-Université d'Evry EMI0006, Evry, France
2. ²INSERM U535, Villejuif, France
3. ³INSERM U472, Villejuif, France

Correspondence: Dr E Bouzigon, INSERM-Université d'Evry EMI0006, Tour Evry 2 – Génopole, 523, Place des Terrasses de l'Agora, 91034 Evry Cedex, France. Tel: +33 1 60 87 38 20; Fax: +33 1 60 87 38 48; E-mail: bouzigon@evry.inserm.fr

Received 24 December 2003; Revised 15 April 2004; Accepted 7 May 2004; Published online 7 July 2004.

Abstract

Asthma is a complex disease, associated with biological and physiological phenotypes including immunoglobulin E (IgE) levels, sum of positive skin prick tests to allergens (SPTQ), eosinophil counts (EOS) and percent predicted forced expiratory volume in 1 s (%FEV₁). We investigated the patterns of familial correlations and the inter-relationships of these four quantitative phenotypes, using the general class D regressive model, in 320 French EGEA nuclear families ascertained through 204 offspring (set A) and 116 parents (set B). Familial correlations of IgE and SPTQ were consistent with a model including no spouse correlation and equal parent–offspring and sib–sib correlations (_PO=_SS=0.25 for IgE and 0.15 for SPTQ), this model being compatible with an additive polygenic model in the whole sample and the two family subsets A and B. Different patterns of familial correlations of EOS and %FEV₁ were observed in these two sets. In set A, the best fitting model included no spouse correlation and equality of parent–offspring and sib–sib correlations (_PO=_SS=0.14 for EOS and 0.23 for %FEV₁). In set B, EOS had only a significant _SS of 0.28, while %FEV₁ had significant _MO of 0.28 and _SS of 0.16. Analysis of shared familial determinants between these phenotypes indicated an overlap of at most 30% in _FO for IgE and SPTQ and in both _FO and _MO for IgE and EOS, while determinants of %FEV₁ and atopy-related phenotypes appear distinct. These results may have implications for further linkage and association studies with genetic markers.