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A Genome-Wide Scan of Pulmonary Function Measures in the National Heart, Lung, and Blood Institute Family Heart Study

Departments of Medicine, Neurology, and Biostatistics, Boston University Schools of Medicine and Public Health, Boston, Massachusetts; Division of Epidemiology, University of Minnesota School of Public Health, Minneapolis, Minnesota; Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina; Pulmonary Division, LDS Hospital; Central Molecular Laboratory, University of Utah, Salt Lake City, Utah; and Division of Biostatistics, Washington University, St. Louis, Missouri

Correspondence and requests for reprints should be addressed to Jemma B. Wilk, D.Sc., Boston University School of Medicine, B-601, 715 Albany Street, Boston, MA 02118. E-mail: jwilk{at}bu.edu

Spirometric measures of pulmonary function exhibited high heritability in the National Heart, Lung, and Blood Institute Family Heart Study. A genome scan of FEV₁, FVC, and the ratio of FEV₁/FVC was performed to identify chromosomal regions influencing these measures. The pulmonary traits were adjusted through multiple linear regression techniques for the effects of age, age², body mass index, height, smoking status, and pack-years of smoking. The distribution of FEV₁/FVC was transformed to account for nonnormality, and standardized residuals were used as the quantitative trait for variance component linkage analysis in GENEHUNTER (Whitehead Institute, Cambridge, MA). The genome scan identified regions on chromosomes 4 and 18 with logarithm of the odds favoring linkage (LOD) scores above 2.5, and these two chromosomes were further evaluated by incorporating additional marker genotyping. The FEV₁/FVC ratio was linked to chromosome 4 around 28 centimorgans (cM; D4S1511) with a LOD score of 3.5, and the transformed ratio was linked to the same region with a LOD of 2.0. FEV₁ and FVC were suggestively linked to regions on chromosome 18 with multipoint LOD scores of 2.4 for FEV₁ and 1.5 for FVC at 31 cM (D18S843) and a LOD of 2.9 for FVC at 79 cM (D18S858).

Key Words: linkage • spirometry • genome

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