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

Abstract

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 Vmax50, 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 [tau(AA) = tau(AB) = tau(BB) = qA and tau(AA) = tau(AB) = tau(BB)] were rejected. The study provides evidence for a single locus influencing airway-parenchymal dysanapsis.

Genome-wide Linkage of Forced Mid-expiratory Flow in Chronic Obstructive Pulmonary Disease

“…Although dysanapsis may be a characteristic of the healthy individual, Green and colleagues also hypothesized that it may represent a susceptibility state for the development of COPD (17). Through segregation analysis, Chen and colleagues recently demonstrated that measures suggestive of dysanaptic lung growth may be under major genetic control (19). Further research is required to determine whether genes within the linkage peaks for FEF 25-75% , FEF 25-75% /FVC, and FEV 1 /FVC are important for lung growth and development and/or early inflammatory effects of smoking on airflow obstruction.…”

Familial aggregation of FEF25-75 and FEF25-75/FVC in families with severe, early onset COPD

“…22 23 Dysanaptic lung growth may predispose to the development of obstructive lung disease 24 25 and may also predict airway hyperresponsiveness. 26 Chen and colleagues 27 have recently investigated whether dysanaptic lung growth has a genetic component. 27 They investigated Vmax 50 /FVC using segregation analysis and suggested that dysanaptic growth of the lung airways to parenchyma is under major gene control.…”

Effects of glutathione S‐transferase M1, T1 and P1 on lung function in asthmatic families

“…Further effects are seen throughout childhood, with early respiratory infections, environmental tobacco smoke [3] and air pollution [4] all associated with reduced lung function growth. The genetic factors associated with lung function in childhood have been less extensively studied but are clearly important [5–7]. Twin studies give heritability estimates as high as 77% for monozygotic twins [8].…”