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

• Published in: Clinical and experimental allergy Vol. 36; no. 11; pp. 1382 - 1390
• Main Authors: Thomsen, S. F., Ulrik, C. S., Kyvik, K. O., Ferreira, M. A. R., Backer, V.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-2006; Blackwell
• Subjects: Adult; airway hyper-responsiveness; Allergic diseases; asthma; Biological and medical sciences; Bronchial Provocation Tests; Diseases in Twins; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genotype; Humans; Hypersensitivity - genetics; Immunopathology; Male; Medical sciences; Multivariate Analysis; Phenotype; Respiratory Sounds; rhinitis; Rhinitis - immunology; skin prick test; Skin Tests; twin study; Twins, Dizygotic; Twins, Monozygotic; Immunopathology; Lung disease; Allergy; Nose disease; Prick test; Rhinitis; Respiratory disease; Exploration; Multivariate analysis; Respiratory system; Asthma; Atopy; Twin; Respiratory tract; Phenotype; Immunology; twin study; airway hyper-responsiveness; Bronchus disease; ENT disease; Genetics; skin prick test; Obstructive pulmonary disease; Skin test
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02512.x

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 (ρA=0.95), wheeze–AHR (ρA=0.85) and rhinitis–posSPT (ρA=0.92), whereas lower genetic correlations were observed for rhinitis–AHR (ρA=0.43) and AHR–posSPT (ρA=0.59). Traits with a high degree of environmental sharing were rhinitis–posSPT (ρE=0.92) and wheeze–posSPT (ρE=0.71), whereas a lower environmental correlation was seen for wheeze–rhinitis (ρE=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.