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An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
Published on: November 3, 2010
Estimating the sensitivity of a genetic test using gene-carrier probability estimates and its application in genetic
1University of Heidelberg, Department of Tropical Hygiene and Public Health, Germany.
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.
Discussion:
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.
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