UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence

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. Green open access

[thumbnail of Menon-U_robust tests for addictive_gene.pdf]
Preview
Text
Menon-U_robust tests for addictive_gene.pdf - Accepted Version

Download (2MB) | Preview

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
Downloads since deposit
94Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item