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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Heritability of lung disease severity in cystic fibrosis.

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 patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV(1) within the last year was used for cross-sectional analysis. FEV(1) 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 monozygous (MZ) twins (approximately 100% gene sharing) with that of dizygous (DZ) twins/siblings (approximately 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. MEASUREMENTS AND MAIN RESULTS: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 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 (measured as body mass index z-score). CONCLUSIONS: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype.[1]

References

  1. Heritability of lung disease severity in cystic fibrosis. Vanscoy, L.L., Blackman, S.M., Collaco, J.M., Bowers, A., Lai, T., Naughton, K., Algire, M., McWilliams, R., Beck, S., Hoover-Fong, J., Hamosh, A., Cutler, D., Cutting, G.R. Am. J. Respir. Crit. Care Med. (2007) [Pubmed]
 
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