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Genomewide Screen for Pulmonary Function in 200 Families Ascertained for Asthma

Department of Pulmonology, and Beatrix Children's Hospital, University Hospital, Groningen; Department of Pulmonary Rehabilitation, Beatrixoord, Haren, The Netherlands; and Center for Human Genomics, Departments of Pediatrics and Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Correspondence and requests for reprints should be addressed to D. S. Postma, M.D., Ph.D., Department of Pulmonology, University Hospital, Hanzeplein 3, 9731 GZ Groningen, The Netherlands. E-mail: d.s.postma{at}int.azg.nl

Changes in pulmonary function are important in determining asthma outcome. Genetic factors may influence airway obstruction in asthma. We performed a genomewide screen in 200 families of probands objectively diagnosed with asthma in the 1960s to identify chromosomal regions related to changes in pre- and postbronchodilator lung function (FEV₁, VC, and FEV₁%VC) and assess influences of early-life smoke exposure. Smoking (pack-years), age, sex, and height were covariates in variance component analyses. Significant evidence for linkage of pre- and postbronchodilator FEV₁%VC was obtained for chromosome 2q32 (LOD,4.9, increasing to 6.03 with additional fine-mapping markers, and 3.2, respectively). Linkage existed for chromosome 5q for pre- and postbronchodilator VC (likelihood of disease [LOD], 1.8 and 2.6, respectively). Results for pre- and postbronchodilator FEV₁ were less significant (LOD, 1.5 and 1.6, chromosomes 11p and 10q, respectively). Results were not affected by passive smoke exposure. There is significant evidence for linkage of FEV₁%VC to chromosome 2q32 in families of probands with asthma, 35 cM proximal from linkage previously observed in families of probands with early-onset chronic obstructive pulmonary disease. Thus, there may be multiple genes on chromosome 2q that are important in determining presence and degree of airflow limitation in families ascertained for obstructive airway disease.

Key Words: asthma • function • genes • linkage • lung

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