title: Estimating the sensitivity of a genetic test using gene-carrier probability estimates and its application in genetic counselling.
abstract: BACKGROUND
  The estimation of the sensitivity of a genetic test is of practical importance. If a 'gold standard' (an exact test) is not available, an estimate of the probability of being a gene carrier may be useful for an individual. This information could be based on individual pedigree and family-history data, and a known genetic model for the disease of interest.
  
  
  METHODS
  We develop a maximum-likelihood estimate of the sensitivity of a genetic test that may be applied in a situation without a 'gold standard', in which an estimate of the probability of being a gene carrier for an individual is available.
  
  
  RESULTS
  A maximum-likelihood estimate for the sensitivity can be obtained through an iterative algorithm. We demonstrate the method using data from a project on familial breast cancer. We further present disease-risk estimates incorporating results from a genetic test with different values of sensitivity, and compare these with disease-risk estimates that are solely based on family-history data.
  
  
  CONCLUSIONS
  We provide a systematic methodology to obtain an estimate of sensitivity of a genetic test when only gene-carrier probability estimates from a genetic model are available. Given a negative result from a genetic test, predictions for lifetime and age-specific disease-risk, accounting for test sensitivity, can then be provided in genetic counselling.
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling / Q000592:standards*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D005821:Genetic Techniques / Q000592:standards*; D006579:Heterozygote; D006801:Humans; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D018570:Risk Assessment / Q000592:standards; D012680:Sensitivity and Specificity