Global test for high-dimensional mediation: Testing groups of potential mediators
AuthorDjordjilovic, Vera; Page, Christian Magnus; Gran, Jon Michael; Nøst, Therese Haugdahl; Sandanger, Torkjel M; Veierød, Marit Bragelien; Thoresen, Magne
We address the problem of testing whether a possibly high‐dimensional vector may act as a mediator between some exposure variable and the outcome of interest. We propose a global test for mediation, which combines a global test with the intersection‐union principle. We discuss theoretical properties of our approach and conduct simulation studies that demonstrate that it performs equally well or better than its competitor. We also propose a multiple testing procedure, ScreenMin, that provides asymptotic control of either familywise error rate or false discovery rate when multiple groups of potential mediators are tested simultaneously. We apply our approach to data from a large Norwegian cohort study, where we look at the hypothesis that smoking increases the risk of lung cancer by modifying the level of DNA methylation.
This is the peer reviewed version of the following article: Djordjilovic, V., Page, C.M., Gran, J.M., Nøst, T.H., Sandanger, T.M., Veierød, M.B. & Thoresen, M. (2019). Global test for high‐dimensional mediation: Testing groups of potential mediators. Statistics in Medicine, 38(18), 3346-3360, which has been published in final form at https://doi.org/10.1002/sim.8199. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.