Statistical Inference for High-Dimensional Pathway Analysis with Multiple Responses

Comput Stat Data Anal. 2022 May:169:107418. doi: 10.1016/j.csda.2021.107418. Epub 2022 Jan 13.

Abstract

Pathway analysis, i.e., grouping analysis, has important applications in genomic studies. Existing pathway analysis approaches are mostly focused on a single response and are not suitable for analyzing complex diseases that are often related with multiple response variables. Although a handful of approaches have been developed for multiple responses, these methods are mainly designed for pathways with a moderate number of features. A multi-response pathway analysis approach that is able to conduct statistical inference when the dimension is potentially higher than sample size is introduced. Asymptotical properties of the test statistic are established and theoretical investigation of the statistical power is conducted. Simulation studies and real data analysis show that the proposed approach performs well in identifying important pathways that influence multiple expression quantitative trait loci (eQTL).

Keywords: 2010 MSC; 62H15; 62P10; Asymptotical distribution; Complex diseases; High dimensional inference; Multivariate responses; Pathway analysis.