Heritability of lung disease severity in cystic fibrosis

Lori L. Vanscoy, Scott M. Blackman, Joseph M. Collaco, Amanda Bowers, Teresa Lai, Kathleen Naughton, Marilyn Algire, Rita McWilliams, Suzanne Beck, Julie Hoover-Fong, Ada Hamosh, Dave Cutler, Garry R. Cutting

Research output: Contribution to journalArticlepeer-review

138 Scopus citations


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 FEV1 within the last year was 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 monozygous (MZ) twins (∼ 100% gene sharing) with that of dizygous (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: 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.

Original languageEnglish (US)
Pages (from-to)1036-1043
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Issue number10
StatePublished - May 15 2007


  • Genetics
  • Pulmonary function

ASJC Scopus subject areas

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


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