Robust inference for variance components models in families ascertained through probands: II. Analysis of spirometric...

Three spirometric measures of pulmonary function were used to estimate genetic and nongenetic components of variance for 781 members of 158 families ascertained through a proband with obstructive pulmonary disease. Forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and the ratio of these two (FEV1/FVC) were adjusted for age, sex, race, smoking, and height and used in a robust approach to estimate variance components after conditioning on the proband's observed value. The best fitting model for both residual FEV1/FVC and FEV1 included an additive genetic component representing 25% and 9% of the variation in these two traits, respectively. In addition, there was a significant correlation between parents in residual FEV1/FVC, and a component shared among full sibs was statistically significant for residual FEV1. No evidence of a genetic component for residual FVC was found in this analysis. Although these results agree with previous reports based on other populations in showing a substantial degree of direct genetic control over spirometric measures of pulmonary function, they also raise the possibility of etiologic heterogeneity.