Case-Control Vs. Case-Only Estimates Of Gene-Environment Interactions With Common And Misclassified Clinical Diagosis

Abstract

Genetic studies provide valuable information to assess if the effect of genetic variants varies by the non-genetic (\"environmental\") variables, what is traditionally defined to be gene-environment interaction. A common complication is that multiple disease states present with the same set of symptoms, and hence share the clinical diagnosis. Because 1) disease states might have distinct genetic bases; and 2) frequencies of the disease states within the clinical diagnosis vary by the environmental variables, analyses of association with the clinical diagnosis as an outcome variable might result in false positive or false negative findings. We develop estimates for assessment of GxE in a case-only study and compare the case-control and case-only estimates. We report extensive simulation studies that evaluate empirical properties of the estimates and show the application to a study of Alzheimers disease.