Published ahead of print on March 1, 2007, doi:10.1164/rccm.200608-1164OC Am. J. Respir. Crit. Care Med., Volume 175, Number 10, May 2007, 1036-1043 A more recent version of this article appeared on May 15, 2007
Submitted on August 16, 2006 Heritability of Lung Disease Severity in Cystic FibrosisLori L Vanscoy1,1 Division of Pediatric Respiratory Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 Division of Pediatric Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 3 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 University of Maryland Medical System, Baltimore, MD, USA, 5 Rutgers University, New Brunswick, NJ, USA, 6 Children's Hospital of Philadelphia, Philadelphia, PA, USA * To whom correspondence should be addressed. E-mail: gcutting{at}jhmi.edu.
Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF),is poorly correlated with mutations in the disease-causing gene indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from CF patients living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of forced expiratory volume in 1 second (FEV1) within the last year as used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e.heritability) was estimated in two ways: by comparing similarity of lung function in MZ twins (~100% gene sharing) to that of DZ twins/siblings (~50% gene sharing) and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: 47 MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82-0.91, p<0.0001) were higher than for DZ twins and siblings (0.50-0.64, p<0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status. Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. Key words: Genetics, Pulmonary Function Testing
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
