Modifier genetics: cystic fibrosis

Annu Rev Genomics Hum Genet. 2005;6:237-60. doi: 10.1146/annurev.genom.6.080604.162254.


Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder in the Caucasian population, affecting about 30,000 individuals in the United States. The gene responsible for CF, the CF transmembrane conductance regulator (CFTR), was identified 15 years ago. Substantial variation in the many aspects of the CF phenotype among individuals with the same CFTR genotype demonstrates that factors independent of CFTR exert considerable influence on outcome in CF. To date, the majority of published studies investigating the cause of disease variability in CF report associations between candidate genes and some aspect of the CF phenotype. However, a definitive modifier gene for CF remains to be identified. Despite the challenges posed by searches for modifier effects, studies of affected twins and siblings indicate that genetic factors play a substantial role in intestinal manifestations. Identifying the factors contributing to variation in pulmonary disease, the primary cause of mortality, remains a challenge for CF research.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Cystic Fibrosis / etiology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Female
  • Genotype
  • Humans
  • Intestines / physiopathology
  • Liver / physiopathology
  • Lung Diseases / etiology
  • Lung Diseases / genetics
  • Lung Diseases / physiopathology
  • Male
  • Pancreas / physiopathology
  • Phenotype
  • Sweat Glands / physiopathology
  • Vas Deferens / abnormalities
  • Vas Deferens / physiopathology


  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator