OTTERS: a powerful TWAS framework leveraging summary-level reference data

Publication date

2023-12

Authors

Dai, Qile
Zhou, Geyu
Võsa, Urmo
Franke, Lude
Battle, Alexis
Teumer, Alexander
Lehtimäki, Terho
Raitakari, Olli T.
Esko, Tõnu
Deelen, Patrick

Editors

Advisors

Supervisors

Document Type

Article

Collections

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License

cc_by

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.

Keywords

General Chemistry, General Biochemistry,Genetics and Molecular Biology, General Physics and Astronomy

Citation

Dai, Q, Zhou, G, Võsa, U, Franke, L, Battle, A, Teumer, A, Lehtimäki, T, Raitakari, O T, Esko, T, Deelen, P & eQTLGen Consortium 2023, 'OTTERS : a powerful TWAS framework leveraging summary-level reference data', Nature Communications, vol. 14, no. 1, 1271. https://doi.org/10.1038/s41467-023-36862-w