Robust tests for additive gene-environment interaction in case-control studies using gene-environment independence
There have been recent proposals advocating the use of additive gene-environment interaction instead of the widely used multiplicative scale, as a more relevant public health measure. Using gene-environment independence enhances statistical power for testing multiplicative interaction in case-control studies. However, under departure from this assumption, substantial bias in the estimates and inflated type I error in the corresponding tests can occur. In this paper, we extend the empirical Bayes (EB) approach previously developed for multiplicative interaction, which trades off between bias and efficiency in a data-adaptive way, to the additive scale. An EB estimator of the relative excess risk due to interaction is derived, and the corresponding Wald test is proposed with a general regression setting under a retrospective likelihood framework. We study the impact of gene-environment association on the resultant test with case-control data. Our simulation studies suggest that the EB approach uses the gene-environment independence assumption in a data-adaptive way and provides a gain in power compared with the standard logistic regression analysis and better control of type I error when compared with the analysis assuming gene-environment independence. We illustrate the methods with data from the Ovarian Cancer Association Consortium.
|ISBN||1476-6256 (Electronic) 0002-9262 (Linking)|
|Authors||Liu, G.; Mukherjee, B.; Lee, S.; Lee, A. W.; Wu, A. H.; Bandera, E. V.; Jensen, A.; Rossing, M. A.; Moysich, K. B.; Chang-Claude, J.; Doherty, J. A.; Gentry-Maharaj, A.; Kiemeney, L.; Gayther, S. A.; Modugno, F.; Massuger, L.; Goode, E. L.; Fridley, B. L.; Terry, K. L.; Cramer, D. W.; Ramus, S. J.; Anton-Culver, H.; Ziogas, A.; Tyrer, J. P.; Schildkraut, J. M.; Kjaer, S. K.; Webb, P. M.; Ness, R. B.; Menon, U.; Berchuck, A.; Pharoah, P. D.; Risch, H.; Pearce, C. L.; Ovarian Cancer Association Consortium|
|Publisher Name||AMERICAN JOURNAL OF EPIDEMIOLOGY|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/28633381|