Exploring the origins of asthma: Lessons from twin studies

Abstract

This thesis explores the contribution of twin studies, particularly those studies originating from the Danish Twin Registry, to the understanding of the aetiology of asthma. First, it is explored how twin studies have established the contribution of genetic and environmental factors to the variation in the susceptibility to asthma, and to the variation in several aspects of the clinical expression of the disease such as its age at onset, its symptomatology, its intermediate phenotypes, and its relationship with other atopic diseases. Next, it is explored how twin studies have corroborated theories explaining asthma's recent increase in prevalence, and last, how these fit with the explanations of the epidemiological trends in other common chronic diseases of modernity.

Fig. 1

Classical twin model of asthma. Note: A classical twin model showing latent additive genetic effects (A), shared environmental effects (C), and non-shared environmental effects (E) on asthma measured in a pair of twins. The arrows pointing from each of the latent factors to the trait (asthma) account for the variation observed in asthma. Additive genetic effects are correlated 1.0 across MZ twins and 0.5 across DZ twins, whereas shared environmental effects, by definition, are correlated 1.0 both across MZ and DZ twins. Non-shared environmental effects are uncorrelated across twin pairs. In cases where non-additive genetic effects can be assumed to contribute to the trait variance (MZ correlation above twice the DZ correlation) the shared environmental variance component is substituted with a non-additive genetic variance component. Non-additive genetic effects are correlated 1.0 across MZ twins and 0.25 across DZ twins.

Fig. 2

Ratio between MZ and DZ concordance rates for asthma obtained from recent population-based twin studies.

Fig. 3

Variance decomposition of asthma obtained from recent population-based twin studies. Note: Proportion of variance (%) in asthma susceptibility due to additive genetic effects (A), shared environmental effects (C), non-additive genetic effects (D), and non-shared environmental effects (E). Variance components sum to 100%. Unadjusted variance components were recalculated from the raw data for Nieminen et al., , using the statistical software Mx [Neale et al., 2006].

Fig. 4

Risk of asthma in the co-twin as a function of the age at onset of asthma in the index twin in Danish twins, 20–71 years of age. Modified from [II].

Fig. 5

Change in prevalence of asthma between 1994 and 2003 among Danish adolescent twins.

Fig. 6

Risk of atopic diseases in Danish twins with and without type 1 diabetes. Note: Prevalence (%) of atopic diseases in child and adolescent twins (left panel) and adult twins (right panel).

Fig. 7

Relationship between asthma and birth weight in Danish twins, 3–9 years of age.

Fig. 8

Relationship between asthma and BMI in Danish twins, 20–71 years of age.