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Eur J Epidemiol. 2015 May;30(5):413-23. doi: 10.1007/s10654-014-9908-1. Epub 2014 Jun 4.

The impact of exposure-biased sampling designs on detection of gene-environment interactions in case-control studies with potential exposure misclassification.

Author information

1
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA, stenzesl@usc.edu.

Abstract

With limited funding and biological specimen availability, choosing an optimal sampling design to maximize power for detecting gene-by-environment (G-E) interactions is critical. Exposure-enriched sampling is often used to select subjects with rare exposures for genotyping to enhance power for tests of G-E effects. However, exposure misclassification (MC) combined with biased sampling can affect characteristics of tests for G-E interaction and joint tests for marginal association and G-E interaction. Here, we characterize the impact of exposure-biased sampling under conditions of perfect exposure information and exposure MC on properties of several methods for conducting inference. We assess the Type I error, power, bias, and mean squared error properties of case-only, case-control, and empirical Bayes methods for testing/estimating G-E interaction and a joint test for marginal G (or E) effect and G-E interaction across three biased sampling schemes. Properties are evaluated via empirical simulation studies. With perfect exposure information, exposure-enriched sampling schemes enhance power as compared to random selection of subjects irrespective of exposure prevalence but yield bias in estimation of the G-E interaction and marginal E parameters. Exposure MC modifies the relative performance of sampling designs when compared to the case of perfect exposure information. Those conducting G-E interaction studies should be aware of exposure MC properties and the prevalence of exposure when choosing an ideal sampling scheme and method for characterizing G-E interactions and joint effects.

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PMID:
24894824
PMCID:
PMC4256150
DOI:
10.1007/s10654-014-9908-1
[Indexed for MEDLINE]
Free PMC Article

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