Asthma and Atopy are Complex Genetic Traits

Asthma is a phenotypically heterogeneous disorder associated with intermittent respiratory symptoms, bronchial hyperresponsiveness, and reversible airflow obstruction (NHLBI 1992; Sheffer et al. 1991). Most individuals with asthma have evidence of bronchial hyperresponsiveness (BHR) and atopy, with elevated total serum IgE, allergen-specific IgE, or skin test reactivity to common allergens. At present, it is not clear whether asthma, BHR, and atopy are clinical manifestations of the same underlying primary defect or whether they share common pathways with distinct primary molecular etiologies. A genetic component to asthma has long been suggested by studies demonstrating increased prevalences of asthma among first degree relatives of asthmatics and greater concordance rates among monozygotic compared to dizygotic twins (Duffy et al. 1990; Edfors-Lubs 1971; Hopp et al. 1988; Longo et al. 1987; Sibbald and Turner-Warwick 1979). Such "clustering" in families is consistent with a genetic etiology, but may also reflect the effects of shared environmental exposures. Thus, familial clustering does not prove a genetic etiology. Although segregation analyses in populations of asthma families have suggested the likelihood of a major genetic component for susceptibility to asthma (Martinez et al. 1994; Townley et al. 1986), direct evidence that susceptibility to asthma is genetically determined requires identifying the specific genes that confer susceptibility to asthma or to an asthma-associated phenotypes, such as BHR or atopy.