Factor analysis of asthma phenotypes from a large collection of Caucasian families

RATIONALE: Asthma is a complex disease and the intricate interplay between genetic and environmental factors underlies the overall phenotype. The genetics of asthma have been studied extensively. A variety of asthma phenotypes have been used in genetic studies and many of these traits are highly correlated, which increases the likelihood of type I error. METHODS: Factor analysis was performed in probands from 1018 families from the Genetics of Asthma International Network (GAIN) study. Data from the respiratory questionnaire, pulmonary function tests, methacholine challenge test, skin prick test and total serum IgE were analyzed to discover the underlying factors that influence these traits. The analysis was repeated using one sibling of the proband from each family. RESULTS: Five interpretable factors were identified: 1.pulmonary function measures, 2.atopy characterized by skin prick test, 3.atopy characterized by self report of allergies, 4. clinical symptoms characteristic of allergic rhinitis and 5.wheeze symptoms. The 5-factor model was verified using sub samples across age, gender and centers. The scores for the five factors were correlated with IgE, PC20 and age, and strongly associated with the asthma disease status diagnosed by a physician. Analysis of within family correlation provides evidence of genetic effects or environmental effects shared by sibs. Linkage analysis was further used to identify the susceptible genetic regions responsible for these latent factors. CONCLUSIONS: Factor analysis of asthma phenotypes identified five interpretable factors, which will provide more insights in the asthma phenotypes originally used in the genetic analysis of the genome scan data.