Familial correlation in the decline of forced expiratory volume in one second

Studies have shown evidence of significant parent-offspring and sibling correlation in FEV₁, but familial aggregation of decline of FEV₁ over time has not been reported. Our study population comprised 392 families enrolled in the Tucson Epidemiological Study of Airway Obstructive Diseases. Subjects were older than 18 yr of age and performed at least 3 pulmonary function tests over 5 to 20 yr. The slope of FEV₁ was calculated for each subject using simple linear regression. Multiple regression models were used to compute standardized residual slope values adjusted for possible confounders. Familial correlation analysis on residual slope values demonstrated no evidence of spousal or parent-offspring correlation. However, sibling pairs were highly correlated (r = 0.256, p < 0.001, n = 166), especially smoking-concordant pairs (r = 0.483, p < 0.01 for ever-smokers, and r = 0.280, p < 0.05 for never-smokers). The residual slopes of smoking-discordant siblings were not significantly correlated (r = 0.031, p < 0.77). Genetic susceptibility to an accelerated rate of decline associated with smoking may be evidenced in the increased correlation among smoking sibling pairs, and in the lack of correlation among smoking-discordant sibling pairs. High sibling correlation in the absence of parent-offspring correlation is compatible with a recessive model of inheritance.