Subset scanning for multi-trait analysis using GWAS summary statistics.

MOTIVATION: Multi-trait analysis has been shown to have greater statistical power than single-trait analysis. Most of the existing multi-trait analysis methods only work with a limited number of traits and usually prioritize high statistical power over identifying relevant traits, which heavily rely on domain knowledge. RESULTS: To handle diseases and traits with obscure etiology, we developed TraitScan, a powerful and fast algorithm that identifies potential pleiotropic traits from a moderate or large number of traits (e.g. dozens to thousands) and tests the association between one genetic variant and the selected traits. TraitScan can handle either individual-level or summary-level GWAS data. We evaluated TraitScan using extensive simulations and found that it outperformed existing methods in terms of both testing power and trait selection when sparsity was low or modest. We then applied it to search for traits associated with Ewing Sarcoma, a rare bone tumor with peak onset in adolescence, among 754 traits in UK Biobank. Our analysis revealed a few promising traits worthy of further investigation, highlighting the use of TraitScan for more effective multi-trait analysis as biobanks emerge. We also extended TraitScan to search and test association with a polygenic risk score and genetically imputed gene expression. AVAILABILITY AND IMPLEMENTATION: Our algorithm is implemented in an R package "TraitScan" available at https://github.com/RuiCao34/TraitScan.

Fast subset scan for multivariate event detection.

We present new subset scan methods for multivariate event detection in massive space-time datasets. We extend the recently proposed 'fast subset scan' framework from univariate to multivariate data, enabling computationally efficient detection of irregular space-time clusters even when the numbers of spatial locations and data streams are large. For two variants of the multivariate subset scan, we demonstrate that the scan statistic can be efficiently optimized over proximity-constrained subsets of locations and over all subsets of the monitored data streams, enabling timely detection of emerging events and accurate characterization of the affected locations and streams. Using our new fast search algorithms, we perform an empirical comparison of the Subset Aggregation and Kulldorff multivariate subset scans on synthetic data and real-world disease surveillance tasks, demonstrating tradeoffs between the detection and characterization performance of the two methods.