1. OTTERS:a powerful TWAS framework leveraging summary-level reference data
- Author
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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, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Biological Psychology, Amsterdam Reproduction & Development, APH - Methodology, APH - Personalized Medicine, Internal Medicine, Tampere University, Department of Clinical Chemistry, and Clinical Medicine
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Multidisciplinary ,1182 Biochemistry, cell and molecular biology ,General Physics and Astronomy ,3111 Biomedicine ,General Chemistry ,Medical Genetics ,General Biochemistry, Genetics and Molecular Biology ,Medicinsk genetik - 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. Godkänd;2023;Nivå 0;2023-04-06 (hanlid);Funder: for more funders see the article https://doi.org/10.1038/s41467-023-36862-w
- Published
- 2023