Gene- and pathway-based association tests for multiple traits with GWAS summary statistics

Summary To identify novel genetic variants associated with complex traits and to shed new insights on underlying biology, in addition to the most popular single SNP-single trait association analysis, it would be useful to explore multiple correlated (intermediate) traits at the gene- or pathway-level by mining existing single GWAS or meta-analyzed GWAS data. For this purpose, we present an adaptive gene-based test and a pathway-based test for association analysis of multiple traits with GWAS summary statistics. The proposed tests are adaptive at both the SNP- and trait-levels; that is, they account for possibly varying association patterns (e.g. signal sparsity levels) across SNPs and traits, thus maintaining high power across a wide range of situations. Furthermore, the proposed methods are general: they can be applied to mixed types of traits, and to Z-statistics or P-values as summary statistics obtained from either a single GWAS or a meta-analysis of multiple GWAS. Our numerical studies with simulated and real data demonstrated the promising performance of the proposed methods. Availability and Implementation The methods are implemented in R package aSPU, freely and publicly available at: https://cran.r-project.org/web/packages/aSPU/. Supplementary information Supplementary data are available at Bioinformatics online.