Liu, G;
Lee, S;
Lee, AW;
Wu, AH;
Bandera, EV;
Jensen, A;
Anne Rossing, M;
... Mukherjee, B; + view all
(2018)
Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence.
American Journal of Epidemiology
, 187
(2)
pp. 366-377.
10.1093/aje/kwx243.
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Abstract
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 the 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. This paper extends the empirical Bayes (EB) approach previously developed for multiplicative interaction that trades off between bias and efficiency in a data-adaptive way, to the additive scale. An EB estimator of Relative Excess Risk due to Interaction is derived and the corresponding Wald test is proposed with 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 power gain compared to the standard logistic regression analysis and better control of Type I error when compared to the analysis assuming gene-environment independence. We illustrate the methods with data from the Ovarian Cancer Association Consortium.
| Type: | Article |
|---|---|
| Title: | Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/aje/kwx243 |
| Publisher version: | http://doi.org/10.1093/aje/kwx243 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Bias-Variance Trade-off, Effect Modification, Empirical Bayes, Genetic Risk Score, Relative Excess Risk, Shrinkage. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1562264 |
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