Major genetic effects on airway-parenchymal dysanapsis of the lung: The Humboldt family study

We examined familial resemblance and performed segregation analysis for the maximal expiratory flow rate at 50% of vital capacity (Vmax₅₀) and the ratio of Vmax₅₀ to forced vital capacity (FVC), based on data from 309 nuclear families with 1,045 individuals in the town of Humboldt, Saskatchewan, in 1993. Vmax₅₀ is considered as an index of airway function and Vmax₅₀/FVC is considered as an index of airway-parenchymal dysanapsis. Both Vmax₅₀ and Vmax₅₀/FVC were preadjusted for host characteristics (age, height, and weight), environmental factors, and history of respiratory symptoms and diseases in four separate groups (mothers, fathers, daughters, and sons). Both Vmax₅₀ and Vmax₅₀/FVC showed low father-mother correlations and significant parent-offspring and sibling-sibling correlations. Segregation analysis indicated that for residual Vmax_50, the model of no-parent-offspring transmission with possible heterogeneity between two generations fitted the data as well as did the general model with arbitrary transmission probabilities. The Mendelian hypothesis for Vmax₅₀ was rejected, which was consistent with our previous findings for other indexes of airway function. For residual Vmax₅₀/FVC, however, a single locus explained all the familial resemblance and both no-parent-offspring-transmission hypotheses [τ(AA) = τ(AB) = τ(BB) = q_A and τ(AA) = τ(AB) = τ(BB)] were rejected. The study provides evidence for a single locus influencing airway-parenchymal dysanapsis. Genet. Epidemiol. 16:95–110, 1999. © 1999 Wiley-Liss, Inc.