Am. J. Respir. Crit. Care Med., Volume 164, Number 9, November 2001, 1655-1659

Heritability of Longitudinal Change in Lung Function
The Framingham Study

DANIEL J. GOTTLIEB, JEMMA B. WILK, MICHAEL HARMON, JANE C. EVANS, OSCAR JOOST, DANIEL LEVY, GEORGE T. O'CONNOR, and RICHARD H. MYERS

Research Service, VA Boston Healthcare System, and Departments of Medicine and Neurology, Boston University School of Medicine, Boston, Massachusetts; and the National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts

There have been multiple reports of heritability of lung function in cross-sectional analysis, but no prior reports of heritability of rate of change in lung function. We examined heritability of rate of change of lung function in families participating in the Framingham Heart Study. Spirometric measures from two time points were used to calculate annualized rate of change in FEV₁, FVC, and FEV₁/FVC ratio, adjusting for the effects of age, height, and weight using multiple linear regression models. Standardized residuals from these models were used as phenotypic variables in variance components analysis to assess effects of smoking and heritable factors on rate of change in lung function. Heritable factors explained a modest proportion of the population variance, with heritability estimates for change in FEV₁, FVC, and ratio of 0.05, 0.18, and 0.13, respectively. Restricting the analysis to subjects concordant for smoking status during the interval over which lung function was measured, the heritability estimates increased to 0.18, 0.39, and 0.14, respectively, among interim smokers. These data suggest that in middle-aged and older persons in the general population, genetic factors contribute modestly to the overall population variance in rate of lung function decline, and further suggest the importance of gene-environment interactions.

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