Segregation analysis of asthma: Recessive major gene component for asthma in relation to history of atopic diseases

Although asthma has a significant heritable component, the mode of inherita nce remains controversial because of the complexity of the disease and the influence of environmental factors. Segregation analysis for asthma are per formed with and without a history of atopic diseases (dermatitis and rhinit is) after adjusting for environmental factors. To investigate whether asthm a may be inherited through a major gene with two alleles, the REGD program of the Statistical Analysis for Genetic Epidemiology (SAGE) package was con ducted in 1,990 individuals from 227 families with at least one asthmatic c hild in a cross-sectional study of respiratory diseases in Southern Taiwan, Other covariates adjusted for included age, sex, current smoking, and envi ronmental tobacco smoking. The hypothesis of Mendelian model and no parent- offspring transmission was rejected. However, when the variables of atopic disease and environmental factors were included in the model as covariates, the models for a two-allele gene with a recessive or codominant inheritanc e could not be rejected, and Akaike's Information Criterion was smaller (1, 377.13) for the recessive model than all of the other models tested, assumi ng a major gene with a population frequency of 0.56 +/- 0.04, However, Mend elian model without family effect was rejected. In conclusion, a history of asthma in parents is a strong risk factor for asthma in offspring. Under t he assumptions of the applied segregation, at least one major gene exists t hat could be a gene involved also in allergy. However, the data suggest tha t a single Locus gene explains a portion of asthma that is related to the h istory of atopic diseases. In addition, a polygenic/multifactorial (genetic and environmental factors) influence with a recessive component inheritanc e may be involved in the pathogenesis of asthma, (C) 2000 Wiley-Liss, Inc.