Am. J. Respir. Crit. Care Med., Volume 165, Number 6, March 2002, 795-799

Genetic Loci Influencing Lung Function
A Genomewide Scan in the Framingham Study

OSCAR JOOST, JEMMA B. WILK, L. ADRIENNE CUPPLES, MICHAEL HARMON, AMANDA M. SHEARMAN, CLINTON T. BALDWIN, GEORGE T. O'CONNOR, RICHARD H. MYERS, and DANIEL J. GOTTLIEB

Boston University School of Medicine and Boston University School of Public Health; Research Service, Boston VAMC, Boston; and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts

Prior studies have found cross-sectional lung function to be highly heritable. In the present study, we used a 10-cM genome-wide scan of 1,578 members of 330 families participating in the Framingham Study to test for linkage of genetic markers to level of lung function as determined by spirometry during middle age. At this age, lung function measures may reflect the effects of genes influencing lung growth and development, as well as of those influencing decline in lung function during adulthood. We performed spirometry on 345 members of the Original Cohort and 1,233 members of the Offspring Cohort of the Framingham Study. The effects of age, height, body mass index, and smoking status on spirometric measures were adjusted through linear regression models created separately for men and women in each cohort. Standardized residuals for FEV₁, FVC, and the ratio of FEV₁ to FVC were obtained from these models. The residual spirometric measures were analyzed for linkage to the genome scan markers through the use of variance component models in the Sequential Oligogenic Linkage Analysis Routines software program. The loci most strongly influencing FEV₁ and FVC colocalized on chromosomes 4, 6, and 21. FEV₁ was most influenced by the locus on chromosome 6 (logarithm of the odds favoring genetic linkage [LOD] = 2.4), whereas chromosome 21 contained markers with the strongest linkage to FVC (LOD = 2.6).

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