Familial correlations and inter-relationships of four asthma-associated quantitative phenotypes in 320 French EGEA families ascertained through asthmatic probands.

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 (rhoPO = rhoSS = 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 (rhoPO = rhoSS = 0.14 for EOS and 0.23 for %FEV1). In set B, EOS had only a significant rhoSS of 0.28, while %FEV1 had significant rhoMO of 0.28 and rhoSS of 0.16. Analysis of shared familial determinants between these phenotypes indicated an overlap of at most 30% in rhoFO for IgE and SPTQ and in both rhoFO and rhoMO 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.