IngentaConnect Multivariate genetic analysis of atopy phenotypes in a selected s...

Abstract:

Summary Background

Atopic traits often co-occur and this can potentially be caused by common aetiological relationships between traits, i.e. a common genetic or a common environmental background. Objective

To estimate to what extent the same genetic and environmental factors influence wheeze, rhinitis, airway hyper-responsiveness (AHR), and positive skin prick test (posSPT) in a sample of adult twins. Methods

Within a sampling frame of 21 162 twin subjects, 20-49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins), who either themselves and/or their co-twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Symptoms of wheeze and rhinitis were obtained by interview; airway responsiveness and skin test reactivity were measured using standard techniques. Correlations in liability between the different traits were estimated and latent factor models of genetic and environmental effects were fitted to the observed data using maximum likelihood methods. Results

The various phenotypic correlations between wheeze, rhinitis, AHR and posSPT were all significant and ranged between 0.50 and 0.86. Traits that showed highest genetic correlations were wheeze-rhinitis (ρ_A=0.95), wheeze-AHR (ρ_A=0.85) and rhinitis-posSPT (ρ_A=0.92), whereas lower genetic correlations were observed for rhinitis-AHR (ρ_A=0.43) and AHR-posSPT (ρ_A=0.59). Traits with a high degree of environmental sharing were rhinitis-posSPT (ρ_E=0.92) and wheeze-posSPT (ρ_E=0.71), whereas a lower environmental correlation was seen for wheeze-rhinitis (ρ_E=0.25). The estimates were corrected for ascertainment and adjusted for age, sex, inhaled corticosteroids and smoking. Conclusions

Different atopic conditions share, to a large extent, a common genetic background. In particular, upper and lower respiratory symptoms seem to be different phenotypic expressions of a common set of genes. These results add new insight into the origins of clinical heterogeneity within atopy and should stimulate the search for pleiotropic genes of importance for these conditions.

Keywords: airway hyper-responsiveness; asthma; rhinitis; skin prick test; twin study

Document Type: Research article

DOI: 10.1111/j.1365-2222.2006.02512.x

Affiliations: 1: Department of Internal Medicine, Bispebjerg Hospital, Copenhagen, Denmark, 2: Department of Cardiology and Respiratory Medicine, Hvidovre Hospital, Copenhagen, Denmark, 3: The Danish Twin Registry, University of Southern Denmark, Odense, Denmark and 4: Queensland Institute of Medical Research, Brisbane, Australia

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Multivariate genetic analysis of atopy phenotypes in a selected sample of twins