학술논문
OTTERS: a powerful TWAS framework leveraging summary-level reference data
Document Type
Author
Dai, Qile; Zhou, Geyu; Zhao, Hongyu; Võsa, Urmo; Franke, Lude; Battle, Alexis; Teumer, Alexander; Lehtimäki, Terho; Raitakari, Olli T.; Esko, Tõnu; Agbessi, Mawussé; Ahsan, Habibul; Alves, Isabel; Andiappan, Anand Kumar; Arindrarto, Wibowo; Awadalla, Philip; Beutner, Frank; Jan Bonder, Marc; Boomsma, Dorret I.; Christiansen, Mark W.; Claringbould, Annique; Deelen, Patrick; Favé, Marie-Julie; Frayling, Timothy; Gharib, Sina A.; Gibson, Greg; Heijmans, Bastiaan T.; Hemani, Gibran; Jansen, Rick; Kähönen, Mika; Kalnapenkis, Anette; Kasela, Silva; Kettunen, Johannes; Kim, Yungil; Kirsten, Holger; Kovacs, Peter; Krohn, Knut; Kronberg, Jaanika; Kukushkina, Viktorija; Kutalik, Zoltan; Lee, Bernett; Loeffler, Markus; Marigorta, Urko M.; Mei, Hailang; Milani, Lili; Montgomery, Grant W.; Müller-Nurasyid, Martina; Nauck, Matthias; Nivard, Michel G.; Penninx, Brenda; Perola, Markus; Pervjakova, Natalia; Pierce, Brandon L.; Powell, Joseph; Prokisch, Holger; Psaty, Bruce M.; Ripatti, Samuli; Rotzschke, Olaf; Rüeger, Sina; Saha, Ashis; Scholz, Markus; Schramm, Katharina; Seppälä, Ilkka; Slagboom, Eline P.; Stehouwer, Coen D. A.; Stumvoll, Michael; Sullivan, Patrick; ‘t Hoen, Peter A. C.; Thiery, Joachim; Tong, Lin; Tönjes, Anke; van Dongen, Jenny; van Iterson, Maarten; van Meurs, Joyce; Veldink, Jan H.; Verlouw, Joost; Visscher, Peter M.; Völker, Uwe; Westra, Harm-Jan; Wijmenga, Cisca; Yaghootkar, Hanieh; Yang, Jian; Zeng, Biao; Zhang, Futao; Epstein, Michael P.; Yang, Jingjing
Source
Nature Communications. 14(1)
Subject
Language
English
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.