The contribution of twin studies to the understanding of the aetiology of asthma and atopic diseases

Abstract

The prevalence of asthma and other atopic diseases has increased markedly during the past decades and the reasons for this are not fully understood. Asthma is still increasing in many parts of the world, notably in developing countries, and this emphasizes the importance of continuing research aimed at studying the aetiological factors of the disease and the causes of its increase in prevalence. Twin studies enable investigations into the genetic and environmental causes of individual variation in multifactorial diseases such as asthma. Thorough insight into these causes is important as this will ultimately guide the development of preventive strategies and targeted therapies. This review explores the contribution of twin studies to the understanding of the aetiology of asthma and atopic diseases. T he prevalence of asthma has increased markedly during the past decades and the reasons for this are not fully understood. Asthma is still increasing in many parts of the world, notably in developing countries and this emphasizes the importance of continuing research aimed at studying the aetiological factors of the disease and the causes of its increase in prevalence (1). Twin studies enable investigations into the genetic and environmental causes of variation in multifactorial diseases such as asthma. The premise of the twin method is that monozygotic (MZ) twins not only share all their genes but also their upbringing and early environment. Conversely , apart from their upbringing and early environment , dizygotic (DZ) twins share an average of only 50% of their segregating genes. Therefore, all phenotypic dissimilarity between MZ twins is assumed to be due to non-shared environmental differences between the twins, whereas dissimilarity between DZ twins is assumed to be due both to genetic and non-shared environmental differences. Consequently, if MZ twins are more similar for asthma than DZ twins, a genetic contribution to the trait can be inferred. However, a caveat to the interpretation of twin studies is the phenomenon of epigenetics; the transcriptional dynamic alterations leading to changes in gene expression, observed as phenotypic dissimilarities not only in DZ twins but also in MZ twins. Understanding of the aetiology of asthma is important as this will ultimately guide the development of preventive strategies and targeted therapies. This review explores the contribution of twin studies to the understanding of the aetiology of asthma with special emphasis on the importance of genetic and environmental factors for the variation in the susceptibility to asthma; on how twin studies have corroborated theories explaining asthma's recent increase in prevalence; and on how these fit with the explanations of the epidemiological trends in other common chronic diseases of modernity. For a more comprehensive review of this topic, the reader is referred to a previous publication (2). Genetic and environmental influence on asthma Several twin studies have examined the heritability of asthma. For MZ twins, concordance rates range is 0.08Á0.66, while for DZ twins the range is 0.05Á0.45. However, as the concordance depends on the prevalence of the disease , and since the studies represent a period in which asthma has increased markedly in prevalence, the ratio between MZ and DZ concordances signals more accurately the genetic influence on asthma (Fig. 1) (3Á12). Most previous studies show that MZ twins are more concordant for asthma than are DZ twins with a ratio between these concordances of around two (12). One small