Risk factors for asthma in adult twins
Authors: Thomsen Simon Francis 
Published: November 2007

Introduction:  This PhD thesis was conducted at the Respiratory and Allergy Research Unit, Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen, Denmark.

Objective:  This study was conducted in a population of adult twins to: (i) determine the incidence of asthma; (ii) identify the risk factors for asthma; and (iii) estimate to what extent genetic and environmental factors influence asthma, wheeze, rhinitis, positive skin‐prick test (posSPT) and airway hyper‐responsiveness (AHR).

Materials and Methods:  The study population was based on the twin cohorts born between 1953 and 1982 that were ascertained from the nationwide Danish Twin Registry. Questionnaire data on multiple traits including asthma and possible risk factors for asthma was collected in 1994 and 2002, defining a population of 19 349 subjects (6090 intact twin pairs) at risk of new asthma. Furthermore, 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 the 2002 questionnaire, were clinically examined.

Results:  The incidence of asthma was 4.5 and 6.4 per 1000 person‐years, respectively, among males and females (Odds Ratio (OR) = 1.49, P < 0.001). There was a positive association between increasing body mass index (BMI) and risk of asthma for both sexes (OR = 1.05 per unit, P < 0.001). A history of hay fever (OR = 4.2 for males and OR = 3.7 for females, P < 0.001), eczema (OR = 3.5 for males and OR = 2.0 for females, P < 0.001) and both (OR = 6.9 for males and OR = 8.0 for females, P < 0.001) were significant predictors of asthma. Physical exercise was weakly associated with asthma (OR for inactivity = 0.35, P = 0.02), whereas smoking and educational status was not significantly associated with asthma. There was a high genetic similarity between asthma and wheeze (genetic correlation, ρA = 0.96), asthma and rhinitis (ρA = 0.94), wheeze and rhinitis (ρA = 0.95), wheeze and AHR (ρA = 0.85), and rhinitis and posSPT (ρA = 0.92), whereas lower genetic correlations were observed between rhinitis and AHR (ρA = 0.43) and between AHR and posSPT (ρA = 0.59). Traits with a high degree of environmental sharing were asthma and wheeze (environmental correlation, ρE = 0.82), rhinitis and posSPT (ρE = 0.92), and wheeze and posSPT (ρE = 0.71), whereas lower environmental correlations were observed between asthma and rhinitis (ρE = 0.19) and between wheeze and rhinitis (ρE = 0.25).

Conclusions:  The incidence of asthma in adulthood is high, especially among females. In both sexes, increasing levels of BMI increase the risk of asthma. A substantial portion of adult‐onset asthma is preceded by hay fever and eczema. Asthma, wheeze, rhinitis, AHR and posSPT share, to a large extent, a common genetic aetiology. In particular, asthma and rhinitis are genetically similar, but environmentally distinct. Furthermore, genetic factors mainly explain the co‐occurrence of asthma and posSPT, and rhinitis and posSPT, whereas asthma, but not rhinitis, is closely genetically related to AHR. Finally, asthma and posSPT, and rhinitis and posSPT show similar environmental architectures. These results provide new insights into the aetiology of asthma and may be used to guide the choice of traits for genetic linkage analysis.