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Published ahead of print on March 13, 2003, doi:10.1164/rccm.200207-755OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 11, June 2003, 1528-1533

A more recent version of this article appeared on June 1, 2003
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Submitted on July 26, 2002
Accepted on March 7, 2003

A Genomewide Scan of Pulmonary Function Measures in the NHLBI Family Heart Study

Jemma B Wilk1*, Anita L DeStefano1, Donna K Arnett2, Stephen S Rich3, Luc Djousse1, Robert O Crapo4, Mark F Leppert5, Michael A Province6, L. Adrienne Cupples1, Daniel J Gottlieb1, and Richard H Myers1

1 Medicine, Neurology, and Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA, USA, 2 Division of Epidemiology, University of Minnesota School of Public Health, Minneapolis, MN, USA, 3 Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA, 4 Pulmonary Division, LDS Hospital, Salt Lake City, UT, USA, 5 Central Molecular Laboratory, University of Utah, Salt Lake City, UT, USA, 6 Division of Biostatistics, Washington University, St. Louis, MO, USA

* To whom correspondence should be addressed. 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 forced expiratory volume in one second (FEV1), forced vital capacity (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 non-normality, and standardized residuals were used as the quantitative trait for variance component linkage analysis in GENEHUNTER. The genome scan identified regions on chromosomes 4 and 18 with 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 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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