Abstract
The number of methods for genome-wide testing of gene-environment (G-E) interactions continues to increase, with the aim of discovering new genetic risk factors and obtaining insight into the disease-gene-environment relationship. The relative performance of these methods, assessed on the basis of family-wise type I error rate and power, depends on underlying disease-gene-environment associations, estimates of which may be biased in the presence of exposure misclassification. This simulation study expands on a previously published simulation study of methods for detecting G-E interactions by evaluating the impact of exposure misclassification. We consider 7 single-step and modular screening methods for identifying G-E interaction at a genome-wide level and 7 joint tests for genetic association and G-E interaction, for which the goal is to discover new genetic susceptibility loci by leveraging G-E interaction when present. In terms of statistical power, modular methods that screen on the basis of the marginal disease-gene relationship are more robust to exposure misclassification. Joint tests that include main/marginal effects of a gene display a similar robustness, which confirms results from earlier studies. Our results offer an increased understanding of the strengths and limitations of methods for genome-wide searches for G-E interaction and joint tests in the presence of exposure misclassification.
Original language | English (US) |
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Pages (from-to) | 237-247 |
Number of pages | 11 |
Journal | American journal of epidemiology |
Volume | 183 |
Issue number | 3 |
DOIs | |
State | Published - Feb 1 2016 |
Keywords
- case-control
- gene discovery
- gene-environment independence
- genome-wide association
- modular methods
- multiple testing
- screening test
- weighted hypothesis test
ASJC Scopus subject areas
- General Medicine