Genetic association testing with multivariate survival phenotypes under interval censoring

Abstract

Set-based genetic association tests provide a powerful framework for detecting genetic effects on complex traits by jointly analyzing multiple genetic variants. Although set-based methods have been developed for interval-censored survival outcomes, existing approaches primarily focus on a single survival phenotype and therefore do not fully use information from multiple correlated outcomes. In this paper, we develop two Weighted V Tests for Multivariate Interval-Censored Data (WV-M-IC), extending the weighted V-statistic framework (Wu et al., 2021) to the joint analysis of multiple correlated interval-censored survival outcomes. The performance of these methods is evaluated through simulation studies, showing that the proposed approaches can provide power gains compared with single-outcome analyses. We apply the proposed methods to the ZOE 2.0 study to investigate dental caries progression in children.