TY - JOUR
T1 - On the use of population-based registries in the clinical validation of genetic tests for disease susceptibility
AU - Yang, Quanhe
AU - Khoury, Muin J.
AU - Coughlin, Steven S.
AU - Sun, Fengzhu
AU - Flanders, W. Dana
PY - 2000
Y1 - 2000
N2 - Purpose: Many new genetic tests for susceptibility to adult-onset diseases are developed on the basis of selected and high-risk groups. Before such tests can be used in medical practice, however, epidemiologic studies must be conducted to evaluate their clinical sensitivity, specificity, and positive predictive value in the general population. For many common adult-onset diseases, this process may take decades of follow-up. Method: We illustrate how clinical validation of new predictive genetic tests can be done retrospectively using case-control studies that are derived from population-based registries of diseases. We use the examples of birth defects and cancer registries to illustrate a hypothetical process by which such tests can be clinically validated. Results: We demonstrate how such epidemiologic studies can be successfully used to derive measures of a test's sensitivity, specificity, positive predictive value, negative predictive value, and of the population attributable fraction of disease due to the disease-susceptibility genes. Under certain assumptions, data derived from population-based case-control studies provide adequate estimates of lifetime risks for disease (penetrance) among people with specified genotypes. Conclusions: With adequate protections of human subjects, studies involving population-based registries of disease will increasingly become valuable in validating the numerous genetic tests that will emerge from advances in human genetic research and the Human Genome Project.
AB - Purpose: Many new genetic tests for susceptibility to adult-onset diseases are developed on the basis of selected and high-risk groups. Before such tests can be used in medical practice, however, epidemiologic studies must be conducted to evaluate their clinical sensitivity, specificity, and positive predictive value in the general population. For many common adult-onset diseases, this process may take decades of follow-up. Method: We illustrate how clinical validation of new predictive genetic tests can be done retrospectively using case-control studies that are derived from population-based registries of diseases. We use the examples of birth defects and cancer registries to illustrate a hypothetical process by which such tests can be clinically validated. Results: We demonstrate how such epidemiologic studies can be successfully used to derive measures of a test's sensitivity, specificity, positive predictive value, negative predictive value, and of the population attributable fraction of disease due to the disease-susceptibility genes. Under certain assumptions, data derived from population-based case-control studies provide adequate estimates of lifetime risks for disease (penetrance) among people with specified genotypes. Conclusions: With adequate protections of human subjects, studies involving population-based registries of disease will increasingly become valuable in validating the numerous genetic tests that will emerge from advances in human genetic research and the Human Genome Project.
KW - Case-control study
KW - Epidemiologic methods
KW - Genetic testing
KW - Registries
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U2 - 10.1097/00125817-200005000-00005
DO - 10.1097/00125817-200005000-00005
M3 - Article
C2 - 11256664
AN - SCOPUS:0034535334
SN - 1098-3600
VL - 2
SP - 186
EP - 192
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 3
ER -