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; Héléna A. Gaspar; Christiaan A. De Leeuw; Jennifer M. Whitehead Pavlides; Loes 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 Bøcker 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 Søholm 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; Céline 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

doi:10.1038/s41467-017-02769-6

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, Héléna 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 Bøcker 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 Søholm 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, Céline 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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 language	English
Article number	989
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-02769-6
Publication status	Published - 1 Dec 2018

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Maier, R. M., Zhu, Z., Lee, S. H., Trzaskowski, M., Ruderfer, D. M., Stahl, E. A., Ripke, S., Wray, N. R., Yang, J., Visscher, P. M., Robinson, M. R., Forstner, A. J., Mcquillin, A., Trubetskoy, V., Wang, W., Wang, Y., Coleman, J. R. I., Gaspar, H. A., De Leeuw, C. A., ... Zammit, S. (2018). Improving genetic prediction by leveraging genetic correlations among human diseases and traits. Nature Communications, 9( 1), Article 989. https://doi.org/10.1038/s41467-017-02769-6

@article{6f92e37535994b32978a20b49e69a2e6,

title = "Improving genetic prediction by leveraging genetic correlations among human diseases and traits",

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.",

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

note = "Funding Information: The University of Queensland group is supported by the Australian Research Council (Discovery Project 160103860 and 160102400), the Australian National Health and Medical Research Council (NHMRC grants 1087889, 1080157, 1048853, 1050218, 1078901, and 1078037) and the National Institute of Health (NIH grants R21ESO25052- 01 and PO1GMO99568). J.Y. is supported by a Charles and Sylvia Viertel Senior Medical Research Fellowship. M.R.R. is supported by the University of Lausanne. We thank all the participants and researchers of the many cohort studies that make this work possible, as well as our colleagues within The University of Queensland{\textquoteright}s Program for Complex Trait Genomics and the Queensland Brain Institute IT team for comments and suggestions and technical support. The UK Biobank research was conducted using the UK Biobank Resource under project 12514. Statistical analyses of PGC data were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Numerous (>100) grants from government agencies along with substantial private and foundation support worldwide enabled the collection of phenotype and genotype data, without which this research would not be possible; grant numbers are listed in primary PGC publications. This study makes use of data from dbGaP (Accession Numbers: phs000090.v3.p1, phs000674.v2.p2, phs000021.v2.p1, phs000167.v1.p1 and phs000017.v3.p1). A full list of acknowledgements to these data sets can be found in Supplementary Note 1. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-017-02769-6",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = " 1",

}

Maier, RM, Zhu, Z, Lee, SH, Trzaskowski, M, Ruderfer, DM, Stahl, EA, Ripke, S, Wray, NR, Yang, J, Visscher, PM, Robinson, MR, Forstner, AJ, Mcquillin, A, Trubetskoy, V, Wang, W, Wang, Y, Coleman, JRI, Gaspar, HA, De Leeuw, CA, Whitehead Pavlides, JM, Olde Loohuis, LM, Pers, TH, Lee, PH, Charney, AW, Dobbyn, AL, Huckins, L, Boocock, J, Giambartolomei, C, Roussos, P, Mullins, N, Awasthi, S, Agerbo, E, Als, TD, Pedersen, CB, Grove, J, Kupka, R, Regeer, EJ, Anjorin, A, Casas, M, Mahon, PB, Allardyce, J, Escott-Price, V, Forty, L, Fraser, C, Kogevinas, M, Frank, J, Streit, F, Strohmaier, J, Treutlein, J, Witt, SH, Kennedy, JL, Strauss, JS, Garnham, J, O'donovan, C, Slaney, C, Steinberg, S, Thorgeirsson, TE, Hautzinger, M, Steffens, M, Perlis, RH, Sánchez-Mora, C, Hipolito, M, Lawson, WB, Nwulia, EA, Levy, SE, Foroud, TM, Jamain, S, Young, AH, Mckay, JD, Albani, D, Zandi, P, Potash, JB, Zhang, P, Raymond Depaulo, J, Bergen, SE, Juréus, A, Karlsson, R, Kandaswamy, R, Mcguffin, P, Rivera, M, Lissowska, J, Cruceanu, C, Lucae, S, Cervantes, P, Budde, M, Gade, K, Heilbronner, U, Pedersen, MG, Morris, DW, Weickert, CS, Weickert, TW, Macintyre, DJ, Lawrence, J, Elvsåshagen, T, Smeland, OB, Djurovic, S, Xi, S, Green, EK, Czerski, PM, Hauser, J, Xu, W, Vedder, H, Oruc, L, Spijker, AT, Gordon, SD, Medland, SE, Curtis, D, Mühleisen, TW, Badner, J, Scheftner, WA, Sigurdsson, E, Schork, NJ, Schatzberg, AF, Bækvad-Hansen, M, Bybjerg-Grauholm, J, Hansen, CS, Knowles, JA, Szelinger, S, Montgomery, GW, Boks, M, Adolfsson, AN, Hoffmann, P, Bauer, M, Pfennig, A, Leber, M, Kittel-Schneider, S, Reif, A, Del-Favero, J, Fischer, SB, Herms, S, Reinbold, CS, Degenhardt, F, Koller, AC, Maaser, A, Ori, A, Dale, AM, Fan, CC, Greenwood, TA, Nievergelt, CM, Shehktman, T, Shilling, PD, Byerley, W, Bunney, W, Alliey-Rodriguez, N, Clarke, TK, Liu, C, Coryell, W, Akil, H, Burmeister, M, Flickinger, M, Li, JZ, Mcinnis, MG, Meng, F, Thompson, RC, Watson, SJ, Zollner, S, Guan, W, Green, MJ, Craig, D, Sobell, JL, Milani, L, Gordon-Smith, K, Knott, SV, Perry, A, Parra, JG, Mayoral, F, Rivas, F, Rice, JP, Barchas, JD, Børglum, AD, Mortensen, PB, Mors, O, Grigoroiu-Serbanescu, M, Bellivier, F, Etain, B, Leboyer, M, Ramos-Quiroga, JA, Agartz, I, Amin, F, Azevedo, MH, Bass, N, Black, DW, Blackwood, DHR, Bruggeman, R, Buccola, NG, Choudhury, K, Cloninger, CR, Corvin, A, Craddock, N, Daly, MJ, Datta, S, Donohoe, GJ, Duan, J, Dudbridge, F, Fanous, A, Freedman, R, Freimer, NB, Friedl, M, Gill, M, Gurling, H, De Haan, L, Hamshere, ML, Hartmann, AM, Holmans, PA, Kahn, RS, Keller, MC, Kenny, E, Kirov, GK, Krabbendam, L, Krasucki, R, Lencz, T, Levinson, DF, Lieberman, JA, Lin, DY, Linszen, DH, Magnusson, PKE, Maier, W, Malhotra, AK, Mattheisen, M, Mattingsdal, M, Mccarroll, SA, Medeiros, H, Melle, I, Milanova, V, Myin-Germeys, I, Neale, BM, Ophoff, RA, Owen, MJ, Pimm, J, Purcell, SM, Puri, V, Quested, DJ, Rossin, L, Sanders, AR, Shi, J, Sklar, P, St Clair, D, Stroup, TS, Van Os, J, Wiersma, D & Zammit, S 2018, 'Improving genetic prediction by leveraging genetic correlations among human diseases and traits', Nature Communications, vol. 9, no. 1, 989. https://doi.org/10.1038/s41467-017-02769-6

TY - JOUR

T1 - Improving genetic prediction by leveraging genetic correlations among human diseases and traits

AU - Maier, Robert M.

AU - Zhu, Zhihong

AU - Lee, Sang Hong

AU - Trzaskowski, Maciej

AU - Ruderfer, Douglas M.

AU - Stahl, Eli A.

AU - Ripke, Stephan

AU - Wray, Naomi R.

AU - Yang, Jian

AU - Visscher, Peter M.

AU - Robinson, Matthew R.

AU - Forstner, Andreas J.

AU - Mcquillin, Andrew

AU - Trubetskoy, Vassily

AU - Wang, Weiqing

AU - Wang, Yunpeng

AU - Coleman, Jonathan R.I.

AU - Gaspar, Héléna A.

AU - De Leeuw, Christiaan A.

AU - Whitehead Pavlides, Jennifer M.

AU - Olde Loohuis, Loes M.

AU - Pers, Tune H.

AU - Lee, Phil H.

AU - Charney, Alexander W.

AU - Dobbyn, Amanda L.

AU - Huckins, Laura

AU - Boocock, James

AU - Giambartolomei, Claudia

AU - Roussos, Panos

AU - Mullins, Niamh

AU - Awasthi, Swapnil

AU - Agerbo, Esben

AU - Als, Thomas D.

AU - Pedersen, Carsten Bøcker

AU - Grove, Jakob

AU - Kupka, Ralph

AU - Regeer, Eline J.

AU - Anjorin, Adebayo

AU - Casas, Miquel

AU - Mahon, Pamela B.

AU - Allardyce, Judith

AU - Escott-Price, Valentina

AU - Forty, Liz

AU - Fraser, Christine

AU - Kogevinas, Manolis

AU - Frank, Josef

AU - Streit, Fabian

AU - Strohmaier, Jana

AU - Treutlein, Jens

AU - Witt, Stephanie H.

AU - Kennedy, James L.

AU - Strauss, John S.

AU - Garnham, Julie

AU - O'donovan, Claire

AU - Slaney, Claire

AU - Steinberg, Stacy

AU - Thorgeirsson, Thorgeir E.

AU - Hautzinger, Martin

AU - Steffens, Michael

AU - Perlis, Roy H.

AU - Sánchez-Mora, Cristina

AU - Hipolito, Maria

AU - Lawson, William B.

AU - Nwulia, Evaristus A.

AU - Levy, Shawn E.

AU - Foroud, Tatiana M.

AU - Jamain, Stéphane

AU - Young, Allan H.

AU - Mckay, James D.

AU - Albani, Diego

AU - Zandi, Peter

AU - Potash, James B.

AU - Zhang, Peng

AU - Raymond Depaulo, J.

AU - Bergen, Sarah E.

AU - Juréus, Anders

AU - Karlsson, Robert

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N1 - Funding Information: The University of Queensland group is supported by the Australian Research Council (Discovery Project 160103860 and 160102400), the Australian National Health and Medical Research Council (NHMRC grants 1087889, 1080157, 1048853, 1050218, 1078901, and 1078037) and the National Institute of Health (NIH grants R21ESO25052- 01 and PO1GMO99568). J.Y. is supported by a Charles and Sylvia Viertel Senior Medical Research Fellowship. M.R.R. is supported by the University of Lausanne. We thank all the participants and researchers of the many cohort studies that make this work possible, as well as our colleagues within The University of Queensland’s Program for Complex Trait Genomics and the Queensland Brain Institute IT team for comments and suggestions and technical support. The UK Biobank research was conducted using the UK Biobank Resource under project 12514. Statistical analyses of PGC data were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. Numerous (>100) grants from government agencies along with substantial private and foundation support worldwide enabled the collection of phenotype and genotype data, without which this research would not be possible; grant numbers are listed in primary PGC publications. This study makes use of data from dbGaP (Accession Numbers: phs000090.v3.p1, phs000674.v2.p2, phs000021.v2.p1, phs000167.v1.p1 and phs000017.v3.p1). A full list of acknowledgements to these data sets can be found in Supplementary Note 1. Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85048198000&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-02769-6

DO - 10.1038/s41467-017-02769-6

M3 - Article

AN - SCOPUS:85048198000

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 989

ER -

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

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