Data-Adaptive Multivariate Test for Genomic Studies Using Fused Lasso

Abstract

In genomic studies, univariate analysis is commonly used to discover susceptible variants. It applies univariate regression for each variant and tests the significance of the regression coefficient or slope parameter. This strategy, however, may miss signals that are jointly detectable with other variants. Multivariate analysis is another popular approach, which tests grouped variants with a predefined group, e.g., based on a gene, pathway, or physical location. However, the power will be diminished if the modeling assumption is not suited to the data. Therefore, data-adaptive testing that relies on fewer modeling assumptions is preferable. Possible approaches include a data-adaptive test proposed by Ueki (2021), which applies to various data-adaptive regression models using a generalization of Yanai’s generalized coefficient of determination. While several regression models are possible choices for the data-adaptive test, this paper focuses on the fused lasso that can count for the effect of adjacent variants and investigates its performance through comparison with other existing tests. Simulation studies demonstrate that the test using fused lasso has a high power compared to the existing tests including the univariate regression test, saturated regression test, SKAT (sequence kernel association test), burden test, SKAT-O (optimized sequence kernel association test), and the tests using lasso, ridge, and elastic net when assuming a similar effect of adjacent variants.