Kin-cohort evaluation of relative risks of genetic variants

The kin-cohort study, an embedded retrospective cohort of first-degree relatives of probands, has been used frequently in conjunction with case-control studies to evaluate penetrance of high-risk genotypes. However, in principle, the kin-cohort approach can be used in conjunction with a case-control study in which family history data are carefully recorded to examine and validate the observed association of any candidate genotype with disease. Its utility for this purpose is governed by the relative efficiency of the kin-cohort analysis to test hypotheses about the relevant genotype-disease odds ratios, which in turn depends strongly on various factors, notably the magnitude of the disease incidence rate and the prevalence of the aberrant genotype. In this study, we compare the efficiencies of the two analytic approaches, case-control vs. kin-cohort, and illustrate the results in the context of cancer epidemiology. The kin-cohort analysis can provide substantial, important supplementary information for relatively common cancers such as breast, lung, colorectal, and prostate, and is also relatively efficient in general for the evaluation of the stronger and more rare genetic risk factors. Genet Epidemiol 24:220-229, 2003.