OTTERS: a powerful TWAS framework leveraging summary-level reference data - Centre for Population Health Research (POPC) - A joint centre by the University of Turku and the municipal authority of the Hospital District of Southwest Finland. The goal of Centre for Population Health Research is to promote health and well-being of society by enhancing research and development work on clinical-epidemiological population research.

Nat Commun. 2023 Mar 7;14(1):1271. doi: 10.1038/s41467-023-36862-w.

ABSTRACT

Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.

PMID:36882394 | PMC:PMC9992663 | DOI:10.1038/s41467-023-36862-w