Improving genetic prediction by leveraging genetic correlations among human diseases and traits

Robert M. Maier, Zhihong Zhu, Sang Hong Lee, Maciej Trzaskowski, Douglas M. Ruderfer, Eli A. Stahl, Stephan Ripke, Naomi R. Wray, Jian Yang, Peter M. Visscher, Matthew R. Robinson, Andreas J. Forstner, Andrew Mcquillin, Vassily Trubetskoy, Weiqing Wang, Yunpeng Wang, Jonathan R. I. Coleman, H. léna A. Gaspar, Christiaan A. de Leeuw, Jennifer M. Whitehead PavlidesLoes M. Olde Loohuis, Tune H. Pers, Phil H. Lee, Alexander W. Charney, Amanda L. Dobbyn, Laura Huckins, James Boocock, Claudia Giambartolomei, Panos Roussos, Niamh Mullins, Swapnil Awasthi, Esben Agerbo, Thomas D. Als, Carsten B. cker Pedersen, Jakob Grove, Ralph Kupka, Eline J. Regeer, Adebayo Anjorin, Miquel Casas, Pamela B. Mahon, Judith Allardyce, Valentina Escott-Price, Liz Forty, Christine Fraser, Manolis Kogevinas, Josef Frank, Fabian Streit, Jana Strohmaier, Jens Treutlein, Stephanie H. Witt, James L. Kennedy, John S. Strauss, Julie Garnham, Claire O'donovan, Claire Slaney, Stacy Steinberg, Thorgeir E. Thorgeirsson, Martin Hautzinger, Michael Steffens, Roy H. Perlis, Cristina Sánchez-Mora, Maria Hipolito, William B. Lawson, Evaristus A. Nwulia, Shawn E. Levy, Tatiana M. Foroud, Stéphane Jamain, Allan H. Young, James D. Mckay, Diego Albani, Peter Zandi, James B. Potash, Peng Zhang, J. Raymond Depaulo, Sarah E. Bergen, Anders Juréus, Robert Karlsson, Radhika Kandaswamy, Peter Mcguffin, Margarita Rivera, Jolanta Lissowska, Cristiana Cruceanu, Susanne Lucae, Pablo Cervantes, Monika Budde, Katrin Gade, Urs Heilbronner, Marianne Giørtz Pedersen, Derek W. Morris, Cynthia Shannon Weickert, Thomas W. Weickert, Donald J. Macintyre, Jacob Lawrence, Torbjørn Elvsåshagen, Olav B. Smeland, Srdjan Djurovic, Simon Xi, Elaine K. Green, Piotr M. Czerski, Joanna Hauser, Wei Xu, Helmut Vedder, Lilijana Oruc, Anne T. Spijker, Scott D. Gordon, Sarah E. Medland, David Curtis, Thomas W. Mühleisen, Judith Badner, William A. Scheftner, Engilbert Sigurdsson, Nicholas J. Schork, Alan F. Schatzberg, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, Christine S. holm Hansen, James A. Knowles, Szabolcs Szelinger, Grant W. Montgomery, Marco Boks, Annelie Nordin Adolfsson, Per Hoffmann, Michael Bauer, Andrea Pfennig, Markus Leber, Sarah Kittel-Schneider, Andreas Reif, Jurgen del-Favero, Sascha B. Fischer, Stefan Herms, C. line S. Reinbold, Franziska Degenhardt, Anna C. Koller, Anna Maaser, Anil Ori, Anders M. Dale, Chun Chieh Fan, Tiffany A. Greenwood, Caroline M. Nievergelt, Tatyana Shehktman, Paul D. Shilling, William Byerley, William Bunney, Ney Alliey-Rodriguez, Toni-Kim Clarke, Chunyu Liu, William Coryell, Huda Akil, Margit Burmeister, Matthew Flickinger, Jun Z. Li, Melvin G. Mcinnis, Fan Meng, Robert C. Thompson, Stanley J. Watson, Sebastian Zollner, Weihua Guan, Melissa J. Green, David Craig, Janet L. Sobell, Lili Milani, Katherine Gordon-Smith, Sarah V. Knott, Amy Perry, José Guzman Parra, Fermin Mayoral, Fabio Rivas, John P. Rice, Jack D. Barchas, Anders D. Børglum, Preben Bo Mortensen, Ole Mors, Maria Grigoroiu-Serbanescu, Frank Bellivier, Bruno Etain, Marion Leboyer, Josep Antoni Ramos-Quiroga, Ingrid Agartz, Farooq Amin, Maria H. Azevedo, Nicholas Bass, Donald W. Black, Douglas H. R. Blackwood, Richard Bruggeman, Nancy G. Buccola, Khalid Choudhury, C. Robert Cloninger, Aiden Corvin, Nicholas Craddock, Mark J. Daly, Susmita Datta, Gary J. Donohoe, Jubao Duan, Frank Dudbridge, Ayman Fanous, Robert Freedman, Nelson B. Freimer, Marion Friedl, Michael Gill, Hugh Gurling, Lieuwe de Haan, Marian L. Hamshere, Annette M. Hartmann, Peter A. Holmans, René S. Kahn, Matthew C. Keller, Elaine Kenny, George K. Kirov, Lydia Krabbendam, Robert Krasucki, Todd Lencz, Douglas F. Levinson, Jeffrey A. Lieberman, Dan-Yu Lin, Don H. Linszen, Patrik K. E. Magnusson, Wolfgang Maier, Anil K. Malhotra, Manuel Mattheisen, Morten Mattingsdal, Steven A. Mccarroll, Helena Medeiros, Ingrid Melle, Vihra Milanova, Inez Myin-Germeys, Benjamin M. Neale, Roel A. Ophoff, Michael J. Owen, Jonathan Pimm, Shaun M. Purcell, Vinay Puri, Digby J. Quested, Lizzy Rossin, Alan R. Sanders, Jianxin Shi, Pamela Sklar, David St Clair, T. Scott Stroup, Jim van Os, Durk Wiersma, Stanley Zammit

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Abstract

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7% for height to 47% for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait.
Original languageEnglish
Article number02769-6
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018

Cite this

Maier, R. M., Zhu, Z., Lee, S. H., Trzaskowski, M., Ruderfer, D. M., Stahl, E. A., ... Zammit, S. (2018). Improving genetic prediction by leveraging genetic correlations among human diseases and traits. Nature Communications, 9(1), [02769-6]. https://doi.org/10.1038/s41467-017-02769-6