Date: 2017-12-01

Time: 15:30-16:30

Location: BURN 1205

Abstract:

Fisher’s method, also known as Fisher’s combined probability test, is commonly used in meta-analyses to combine p-values from the same test applied to K independent samples to evaluate a common null hypothesis. Here we propose to use it to combine p-values from different tests applied to the same sample in two settings: when jointly analyzing multiple genetic variants in set-based genetic association studies, or when jointly capturing main and interaction effects in the presence of missing one of the interacting variables. In the first setting, we show that many existing methods (e.g. the so called burden test and SKAT) can be classified into a class of linear statistics and another class of quadratic statistics, where each class is powerful only in part of the high-dimensional parameter space. In the second setting, we show that the class of scale-tests for heteroscedasticity can be utilized to indirectly identify unspecified interaction effects, complementing the class of location-tests designed for detecting main effects only. In both settings, we show that the two classes of tests are asymptotically independent of each other under the global null hypothesis. Thus, we can evaluate the significance of the resulting Fisher’s test statistic using the chi-squared distribution with four degrees of freedom; this is a desirable feature for analyzing big data. In addition to analytical results, we provide empirical evidence to show that the new class of joint test is not only robust but can also have better power than the individual tests. This is based on join work with formal graduate students Andriy Derkach (Derkach et al. 2013, Genetic Epidemiology; Derkach et al. 2014, Statistical Science) and David Soave (Soave et al. 2015, The American Journal of Human Genetics; Soave and Sun 2017, Biometrics).

Speaker

Lei Sun is Professor from the Department of Statistical Sciences and Science Division of Biostatistics, Dalla Lana School of Public Health at the University of Toronto