Genomewide screen for pulmonary function in 200 families ascertained for asthma

Dirkje S. Postma, Deborah A. Meyers, Hajo Jongepier, Timothy D. Howard, Gerard H. Koppelman, Eugene R. Bleecker

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)446-452
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume172
Issue number4
DOIs
StatePublished - Aug 15 2005
Externally publishedYes

Keywords

  • Asthma
  • Function
  • Genes
  • Linkage
  • Lung

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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