Candidate genes and the genetic epidemiology of asthma.

Abstract

Genetic disposition and environmental factors are thought to determine the development of asthma and other allergic diseases. It was recognised a long time ago that asthma runs in families and that a positive family history of asthma in parents or siblings represents a strong risk factor for the development of asthma. These clinical observations were confirmed by twin studies which play an important role in determining the contribution of genetic as well as environmental factors in the development of a disease. In the case of asthma the contribution of genetic factors towards the development of the disease was estimated to range from 30% to 75% in twin studies.1 To further determine the pattern of asthma inheritance, segregation studies have been performed. With this method the distribution of a disease in families is compared to the expected distribution in different models comprising genetic (e.g., dominant or recessive inheritance) and/or environmental factors. From these studies it seems most likely that the development of asthma is influenced by multiple genes exerting relatively small effects characteristic for a complex, polygenic disease. Furthermore, intermediate phenotypes associated with asthma such as eosinophilia and elevated serum IgE levels may follow different patterns of inheritance which fit better with models involving one or two major gene loci responsible for the observed pattern of trait distribution. Thus, it is still a matter of debate how many genes contribute to the development