Efficient designs of gene–environment interaction studies: implications of Hardy–Weinberg equilibrium and gene–environment independence
Year: 2012
Type: article
Abstract: It is important to investigate whether genetic susceptibility variants exercise the same effects in populations that are differentially exposed to environmental risk factors. Here, we assess the power of four two-stage case-control design strategies for assessing multiplicative gene-environment (G-E) interactions or for assessing genetic or environmental effects in the presence of G-E interactions. We considered a di-allelic single nucleotide polymorphism G and a binary environmental variable E under the constraints of G-E independence and Hardy-Weinberg equilibrium and used the Wald statistic for all tests. We concluded that (i) for testing G-E interactions or genetic effects in the presence of G-E interactions when data for E are fully available, it is preferable to ascertain data for G in a subsample of cases with similar numbers of exposed and unexposed and a random subsample of controls; and (ii) for testing G-E interactions or environmental effects in the presence of G-E interactions when data for G are fully available, it is preferable to ascertain data for E in a subsample of cases that has similar numbers for each genotype and a random subsample of controls. In addition, supplementing external control data to an existing case-control sample leads to improved power for assessing effects of G or E in the presence of G-E interactions.
Source: Statistics in Medicine
DOI: 10.1002/sim.4460
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2151917757