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

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 JR, 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 DH, 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 PK, 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)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 9

Article Number: 989

Journal Issue: 1

DOI: 10.1038/s41467-017-02769-6

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.

Involved external institutions

University of Queensland Australia (AU) Vanderbilt University United States (USA) (US) Icahn School of Medicine at Mount Sinai United States (USA) (US) King’s College London United Kingdom (GB) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) The Jane and Terry Semel Institute for Neuroscience and Human Behavior United States (USA) (US) Boston Children's Hospital United States (USA) (US) Eli and Edythe L. Broad Institute of MIT and Harvard United States (USA) (US) Universität Basel Switzerland (CH) University College London (UCL) United Kingdom (GB) Charité - Universitätsmedizin Berlin Germany (DE) Massachusetts General Hospital United States (USA) (US) Mario Negri Institute for Pharmacological Research (IRCCS) / Istituto di Ricerche Farmacologiche Mario Negri Italy (IT) Johns Hopkins University (JHU) United States (USA) (US) Johns Hopkins Hospital United States (USA) (US) Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona Spain (ES) Cardiff University United Kingdom (GB) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron Spain (ES) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) Psychiatrisches Krankenhaus Rickling Germany (DE) Erasmus University Medical Center (MC) Netherlands (NL) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Karolinska Institute Sweden (SE) Trinity College Dublin Ireland (IE) Neuroscience Research Australia NeuRA Australia (AU) University of New South Wales (UNSW) Australia (AU) University of Edinburgh United Kingdom (GB) North East London NHS Foundation Trust United Kingdom (GB) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) McGill University Health Centre (MUHC) / Centre universitaire de santé McGill Canada (CA) Klinikum der Universität München (LMU Klinikum) Germany (DE) Universitätsklinikum Göttingen Germany (DE) Scripps Research Institute (TSRI) United States (USA) (US) Stanford University United States (USA) (US) Statens Serum Institut Denmark (DK) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) Umeå University Sweden (SE) Universitätsklinikum Köln Germany (DE) University Of Worcester United Kingdom (GB) University of Minnesota (UMN) United States (USA) (US) VA San Diego Healthcare System United States (USA) (US) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) University of California San Francisco (UCSF) United States (USA) (US) University of Southern California (USC) United States (USA) (US) University of Antwerp / Universiteit Antwerpen Belgium (BE) University of Chicago United States (USA) (US) University of Illinois at Chicago United States (USA) (US) University of Iowa Hospitals and Clinics (UIHC) United States (USA) (US) University of Michigan United States (USA) (US) Washington University in St. Louis United States (USA) (US) Weill Cornell Medicine United States (USA) (US) Aarhus University Denmark (DK) Aarhus University Hospital / Aarhus Universitetshospital Denmark (DK) Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Spain (ES) Universidade de Coimbra Portugal (PT) University of Iowa United States (USA) (US) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) University of North Carolina at Chapel Hill United States (USA) (US) Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra Netherlands (NL) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) Louisiana State University Health Sciences Center United States (USA) (US) Martin-Luther-Universität Halle-Wittenberg (MLU) Germany (DE) University of California Los Angeles (UCLA) United States (USA) (US) Ruprecht-Karls-Universität Heidelberg Germany (DE) University of Toronto Canada (CA) Centre for Addiction and Mental Health (CAMH) Canada (CA) Keck School of Medicine of USC United States (USA) (US) University of Oslo Norway (NO) Aleksandrovska University Hospital / университетска болница "Александровска" Bulgaria (BG) University of Galway (NUIG) / Ollscoil na Gaillimhe Ireland (IE) NorthShore University HealthSystem United States (USA) (US) London School of Hygiene and Tropical Medicine United Kingdom (GB) Georgetown University United States (USA) (US) University of Colorado Anschutz Medical Campus United States (USA) (US) Zucker Hillside Hospital United States (USA) (US) University of Bergen / Universitetet i Bergen Norway (NO) Howard University Hospital (HUH) / Freedmen's Hospital United States (USA) (US) HudsonAlpha United States (USA) (US) Indiana University – Purdue University Indianapolis United States (USA) (US) Université Paris Cité France (FR) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) Maastricht University Netherlands (NL) Lundbeck Foundation Initiative for Integrative Psychiatric Research Denmark (DK) Berkshire Healthcare NHS Foundation Trust United Kingdom (GB) Instituto de Salud Global de Barcelona (ISGlobal) Spain (ES) Universidad de Granada Spain (ES) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie) Germany (DE) University of Oxford United Kingdom (GB) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) University of California Irvine United States (USA) (US) University of Tartu Estonia (EE) Emory University United States (USA) (US) Dalhousie University Canada (CA) deCODE genetics Iceland (IS) Eberhard Karls Universität Tübingen Germany (DE) Pfizer, Inc. United States (USA) (US) Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) / Federal Institute for Drugs and Medical Devices Germany (DE) Rush University United States (USA) (US) University of Colorado at Boulder United States (USA) (US) Cardiovascular Research Foundation United States (USA) (US) University of Aberdeen United Kingdom (GB) National Cancer Institute (NCI) United States (USA) (US)

How to cite

APA:

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). https://doi.org/10.1038/s41467-017-02769-6

MLA:

Maier, Robert M., et al. "Improving genetic prediction by leveraging genetic correlations among human diseases and traits." Nature Communications 9.1 (2018).

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