title: 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.
authors.affiliation: INSERM-Université d'Evry EMI0006, Evry, France. bouzigon@evry.inserm.fr
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bouzigon
authors.forename: Valérie
authors.initials: V
authors.lastname: Chaudru
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Carpentier
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Dizier
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Oryszczyn
authors.forename: Jean
authors.initials: J
authors.lastname: Maccario
authors.forename: Francine
authors.initials: F
authors.lastname: Kauffmann
authors.forename: Florence
authors.initials: F
authors.lastname: Demenais
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001249:Asthma / Q000235:genetics*; D001722:Birth Order; D002648:Child; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D010641:Phenotype; D012044:Regression Analysis; D012737:Sex Factors; D012907:Smoking
chemical_list: D007073:Immunoglobulin E