Quantification of the relative contribution of environmental and genetic factors to variation in cystic fibrosis lung function.
OBJECTIVE
To assess the relative contributions of environmental and genetic factors to variation in cystic fibrosis (CF) lung disease.


METHODS
Genetic and environmental contributions were quantified by use of intrapair correlations and differences in CF-specific forced expiratory volume in 1 second measures from 134 monozygous twins and 272 dizygous twins and siblings while in different living environments (ie, living with parents vs living alone), as well as by use of intraindividual differences in pulmonary function from a separate group of 80 siblings.


RESULTS
Pulmonary function among monozygous twins was more similar than among dizygous twin and sibling pairs, regardless of living environment, affirming the role of genetic modifiers in CF pulmonary function. Regression modeling revealed that genetic factors account for 50% of pulmonary function variation, unique environmental or stochastic factors (36%), and shared environmental factors (14%; P < .0001). The intraindividual analysis produced similar estimates for the contributions of the unique and shared environment. The shared environment effects appeared primarily because of living with a sibling with CF (P = .003), rather than factors within the parental household (P = .310).


CONCLUSIONS
Genetic and environmental factors contribute equally to pulmonary function variation in CF. Environmental effects are dominated by unique and stochastic effects rather than common exposures.
Collaco
J Michael
JM
Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins University, Baltimore, MD 21205, USA.
Blackman
Scott M
SM
McGready
John
J
Naughton
Kathleen M
KM
Cutting
Garry R
GR
D000293:Adolescent; D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D055815:Young Adult