Genomewide screen for pulmonary function in 200 families ascertained for asthma

Area of Science:

• Pulmonary Medicine
• Genetics
• Epidemiology

Background:

• Pulmonary function changes are critical for asthma outcomes.
• Genetic factors are suspected to influence airway obstruction in asthma patients.

Purpose of the Study:

• To conduct a genomewide screen in families with asthma to identify chromosomal regions linked to lung function.
• To assess the influence of early-life smoke exposure on these genetic linkages.

Main Methods:

• Genome-wide screening of 200 families with objectively diagnosed asthma.
• Variance component analyses were used, with covariates including smoking history, age, sex, and height.
• Analysis focused on pre- and postbronchodilator lung function measures: FEV1, VC, and FEV1%VC.

Main Results:

• Significant evidence of linkage for pre- and postbronchodilator FEV1%VC was found on chromosome 2q32 (LOD scores up to 6.03).
• Linkage for pre- and postbronchodilator VC was observed on chromosome 5q (LOD scores 1.8 and 2.6).
• Results for FEV1 showed less significant linkage on chromosomes 11p and 10q. Early-life smoke exposure did not affect the findings.

Conclusions:

• There is strong evidence linking chromosome 2q32 to FEV1%VC in families with asthma.
• This region is located near a previously identified linkage for early-onset chronic obstructive pulmonary disease.
• Multiple genes on chromosome 2q may play a role in determining airflow limitation severity in obstructive airway diseases.