Abstract

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, pFDR: 0.049 to 1.28 × 10−14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.

Depression is correlated with many brain-related traits. Here, Shen et al. perform phenome-wide association studies of a depression polygenic risk score (PRS) and find associations with 51 behavioural and 26 neuroimaging traits which are further followed up on using Mendelian randomization and mediation analyses.

Details

Title
A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank
Author
Shen Xueyi 1   VIAFID ORCID Logo  ; Howard, David M 2   VIAFID ORCID Logo  ; Adams, Mark J 1   VIAFID ORCID Logo  ; David, Hill W 3 ; Toni-Kim, Clarke 1 ; McIntosh, Andrew M 4 ; Deary, Ian J 3 ; Wray, Naomi R 5 ; Ripke Stephan 6 ; Mattheisen Manuel 7 ; Trzaskowski Maciej 8 ; Byrne, Enda M 8 ; Abdellaoui Abdel 9 ; Agerbo Esben 10 ; Air, Tracy M 11 ; Andlauer Till F M 12 ; Silviu-Alin, Bacanu 13 ; Bækvad-Hansen, Marie 14 ; Beekman Aartjan T F 15 ; Bigdeli, Tim B 16 ; Binder, Elisabeth B 17 ; Bryois Julien 18 ; Buttenschøn, Henriette N 19 ; Jonas, Bybjerg-Grauholm 14 ; Cai Na 20 ; Castelao Enrique 21 ; Christensen, Jane Hvarregaard 22 ; Coleman, Jonathan R, I 23 ; Colodro-Conde Lucía 24 ; Couvy-Duchesne Baptiste 25 ; Craddock, Nick 26 ; Crawford, Gregory E 27 ; Davies, Gail 28 ; Degenhardt Franziska 29 ; Derks, Eske M 24 ; Direk Nese 30 ; Dolan, Conor V 9 ; Dunn, Erin C 31 ; Eley, Thalia C 23 ; Escott-Price, Valentina 32 ; Kiadeh Farnush Farhadi Hassan 33 ; Finucane, Hilary K 34 ; Foo, Jerome C 35 ; Forstner, Andreas J 36 ; Frank, Josef 35 ; Gaspar, Héléna A 23 ; Gill, Michael 37 ; Goes, Fernando S 38 ; Gordon, Scott D 24 ; Grove Jakob 39 ; Hall, Lynsey S 40 ; Hansen, Christine Søholm 14 ; Hansen, Thomas F 41 ; Herms, Stefan 42 ; Hickie, Ian B 43 ; Hoffmann, Per 42 ; Homuth Georg 44 ; Horn, Carsten 45 ; Jouke-Jan, Hottenga 9 ; Hougaard, David M 46 ; Ising Marcus 47 ; Jansen, Rick 15 ; Jones, Ian 48 ; Jones, Lisa A 49 ; Jorgenson, Eric 50 ; Knowles, James A 51 ; Kohane, Isaac S 52 ; Kraft, Julia 53 ; Kretzschmar, Warren W 54 ; Kutalik Zoltán 55 ; Li, Yihan 54 ; Lind, Penelope A 24 ; MacIntyre, Donald J 56 ; MacKinnon, Dean F 38 ; Maier, Robert M 57 ; Maier, Wolfgang 58 ; Marchini, Jonathan 59 ; Mbarek Hamdi 9 ; McGrath, Patrick 60 ; McGuffin, Peter 23 ; Medland, Sarah E 24 ; Mehta Divya 61 ; Middeldorp, Christel M 62 ; Mihailov Evelin 63 ; Milaneschi Yuri 15 ; Milani Lili 63 ; Mondimore, Francis M 38 ; Montgomery, Grant W 8 ; Mostafavi, Sara 64 ; Mullins, Niamh 23 ; Nauck Matthias 65 ; Ng, Bernard 66 ; Nivard, Michel G 9 ; Nyholt Dale R 67 ; O’Reilly Paul F 23 ; Oskarsson Hogni 68 ; Owen, Michael J 48 ; Painter, Jodie N 24 ; Pedersen, Carsten Bøcker 10 ; Pedersen, Marianne Giørtz 10 ; Peterson, Roseann E 69 ; Pettersson, Erik 18 ; Peyrot, Wouter J 15 ; Pistis Giorgio 21 ; Posthuma Danielle 70 ; Quiroz, Jorge A 71 ; Qvist Per 22 ; Rice, John P 72 ; Riley, Brien P 13 ; Rivera, Margarita 73 ; Mirza, Saira Saeed 74 ; Schoevers, Robert 75 ; Schulte, Eva C 76 ; Shen, Ling 50 ; Shi, Jianxin 77 ; Shyn, Stanley I 78 ; Sigurdsson Engilbert 79 ; Sinnamon Grant C B 80 ; Smit, Johannes H 15 ; Smith, Daniel J 81 ; Stefansson Hreinn 82 ; Steinberg, Stacy 82 ; Streit Fabian 35 ; Strohmaier, Jana 35 ; Tansey, Katherine E 83 ; Teismann Henning 84 ; Teumer, Alexander 85 ; Thompson, Wesley 86 ; Thomson, Pippa A 87 ; Thorgeirsson Thorgeir E 88 ; Traylor, Matthew 89 ; Treutlein Jens 35 ; Trubetskoy Vassily 53 ; Uitterlinden, Andrés G 90 ; Umbricht, Daniel 91 ; Auwera Sandra Van der 92 ; van Hemert Albert M 93 ; Viktorin, Alexander 18 ; Visscher, Peter M 5 ; Wang, Yunpeng 94 ; Webb, Bradley T 95 ; Weinsheimer, Shantel Marie 96 ; Wellmann Jürgen 84 ; Willemsen Gonneke 9 ; Witt, Stephanie H 35 ; Wu, Yang 8 ; Xi, Hualin S 97 ; Yang, Jian 98 ; Zhang Futao 8 ; Arolt Volker 99 ; Baune, Bernhard T 100 ; Berger, Klaus 84 ; Boomsma Dorret I 9 ; Cichon Sven 101 ; Dannlowski Udo 99 ; de Geus E J C 102 ; Raymond, DePaulo J 38 ; Domenici Enrico 103 ; Domschke Katharina 104 ; Tõnu, Esko 105 ; Grabe, Hans J 92 ; Hamilton, Steven P 106 ; Hayward, Caroline 107 ; Heath, Andrew C 72 ; Kendler, Kenneth S 13 ; Kloiber, Stefan 108 ; Lewis, Glyn 109 ; Li, Qingqin S 110 ; Lucae Susanne 47 ; Madden Pamela A F 72 ; Magnusson, Patrik K 18 ; Martin, Nicholas G 24 ; Metspalu Andres 111 ; Mors Ole 112 ; Mortensen, Preben Bo 113 ; Müller-Myhsok Bertram 114 ; Nordentoft Merete 115 ; Nöthen, Markus M 29 ; O’Donovan Michael C 48 ; Paciga, Sara A 116 ; Pedersen, Nancy L 18 ; Penninx Brenda W J H 15 ; Perlis, Roy H 117 ; Porteous, David J 87 ; Potash, James B 118 ; Preisig, Martin 21 ; Rietschel Marcella 35 ; Schaefer, Catherine 50 ; Schulze, Thomas G 119 ; Smoller, Jordan W 31 ; Stefansson Kari 120 ; Tiemeier Henning 121 ; Uher Rudolf 122 ; Völzke Henry 85 ; Weissman, Myrna M 123 ; Werge, Thomas 124 ; Lewis, Cathryn M 125 ; Levinson, Douglas F 126 ; Breen Gerome 127 ; Børglum, Anders D 22 ; Sullivan, Patrick F 128 ; Whalley, Heather C 1   VIAFID ORCID Logo 

1  University of Edinburgh, Division of Psychiatry, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
2  University of Edinburgh, Division of Psychiatry, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); King’s College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
3  University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Department of Psychology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
4  University of Edinburgh, Division of Psychiatry, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Department of Psychology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
5  The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); The University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
6  Massachusetts General Hospital, Analytic and Translational Genetics Unit, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Universitätsmedizin Berlin Campus Charité Mitte, Department of Psychiatry and Psychotherapy, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662); Broad Institute, Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34) 
7  University of Wurzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Wurzburg, Germany (GRID:grid.8379.5) (ISNI:0000 0001 1958 8658); Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Aarhus University, Department of Biomedicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
8  The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
9  Vrije Universiteit Amsterdam, Dept of Biological Psychology & EMGO+Institute for Health and Care Research, Amsterdam, Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
10  Aarhus University, Centre for Integrated Register-based Research, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Aarhus University, National Centre for Register-Based Research, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300) 
11  University of Adelaide, Discipline of Psychiatry, Adelaide, Australia (GRID:grid.1010.0) (ISNI:0000 0004 1936 7304) 
12  Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095); Technical University of Munich, Department of Neurology, Klinikum rechts der Isar, Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966) 
13  Virginia Commonwealth University, Department of Psychiatry, Richmond, USA (GRID:grid.224260.0) (ISNI:0000 0004 0458 8737) 
14  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Statens Serum Institut, Center for Neonatal Screening, Department for Congenital Disorders, Copenhagen, Denmark (GRID:grid.6203.7) (ISNI:0000 0004 0417 4147) 
15  Vrije Universiteit Medical Center and GGZ inGeest, Department of Psychiatry, Amsterdam, Netherlands (GRID:grid.16872.3a) (ISNI:0000 0004 0435 165X) 
16  Virginia Commonwealth University, Department of Psychiatry, Richmond, USA (GRID:grid.224260.0) (ISNI:0000 0004 0458 8737); Virginia Institute for Psychiatric and Behavior Genetics, Richmond, USA (GRID:grid.224260.0) 
17  Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095); Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
18  Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
19  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University, Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Aarhus University, iSEQ, Centre for Integrative Sequencing, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
20  Wellcome Trust Sanger Institute, Human Genetics, Cambridge, Great Britain (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382); European Bioinformatics Institute (EMBL-EBI), Statistical genomics and systems genetics, Cambridge, Great Britain (GRID:grid.225360.0) (ISNI:0000 0000 9709 7726) 
21  University Hospital of Lausanne, Department of Psychiatry, Prilly, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662) 
22  Aarhus University, Department of Biomedicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University, iSEQ, Centre for Integrative Sequencing, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
23  King’s College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
24  QIMR Berghofer Medical Research Institute, Genetics and Computational Biology, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395) 
25  The University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); The University of Queensland, Centre for Advanced Imaging, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
26  Cardiff University, Psychological Medicine, Cardiff, Great Britain (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670) 
27  Duke University, Center for Genomic and Computational Biology, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961); Duke University, Department of Pediatrics, Division of Medical Genetics, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961) 
28  University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
29  University of Bonn, School of Medicine & University Hospital Bonn, Institute of Human Genetics, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
30  Erasmus MC, Epidemiology, Rotterdam, Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Dokuz Eylul University School Of Medicine, Psychiatry, Izmir, Turkey (GRID:grid.21200.31) (ISNI:0000 0001 2183 9022) 
31  Massachusetts General Hospital, Department of Psychiatry, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Broad Institute, Stanley Center for Psychiatric Research, Cambridge, USA (GRID:grid.66859.34) 
32  Cardiff University, Neuroscience and Mental Health, Cardiff, Great Britain (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670) 
33  University of British Columbia, Bioinformatics, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
34  Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Massachusetts Institute of Technology, Department of Mathematics, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786) 
35  Heidelberg University, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Mannheim, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373) 
36  University of Bonn, School of Medicine & University Hospital Bonn, Institute of Human Genetics, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300); University of Basel, Department of Psychiatry (UPK), Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642); University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642); University of Marburg, Centre for Human Genetics, Marburg, Germany (GRID:grid.10253.35) (ISNI:0000 0004 1936 9756) 
37  Trinity College Dublin, Department of Psychiatry, Dublin, Ireland (GRID:grid.8217.c) (ISNI:0000 0004 1936 9705) 
38  Johns Hopkins University, Psychiatry & Behavioral Sciences, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
39  Aarhus University, Department of Biomedicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University, iSEQ, Centre for Integrative Sequencing, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Aarhus University, Bioinformatics Research Centre, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
40  University of Edinburgh, Division of Psychiatry, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); Newcastle University, Institute of Genetic Medicine, Newcastle upon Tyne, Great Britain (GRID:grid.1006.7) (ISNI:0000 0001 0462 7212) 
41  Rigshospitalet, Danish Headache Centre, Department of Neurology, Glostrup, Denmark (GRID:grid.475435.4); Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836); The Lundbeck Foundation Initiative for Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300) 
42  University of Bonn, School of Medicine & University Hospital Bonn, Institute of Human Genetics, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300); University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642) 
43  University of Sydney, Brain and Mind Centre, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
44  University Medicine and Ernst Moritz Arndt University Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, Greifswald, Germany (GRID:grid.5603.0) 
45  F. Hoffmann-La Roche Ltd, Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland (GRID:grid.417570.0) (ISNI:0000 0004 0374 1269) 
46  Vrije Universiteit Amsterdam, Dept of Biological Psychology & EMGO+Institute for Health and Care Research, Amsterdam, Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095) 
47  Max Planck Institute of Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095) 
48  Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, Great Britain (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670) 
49  University of Worcester, Department of Psychological Medicine, Worcester, Great Britain (GRID:grid.189530.6) (ISNI:0000 0001 0679 8269) 
50  Kaiser Permanente Northern California, Division of Research, Oakland, USA (GRID:grid.280062.e) (ISNI:0000 0000 9957 7758) 
51  University of Southern California, Psychiatry & The Behavioral Sciences, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
52  Harvard Medical School, Department of Biomedical Informatics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Brigham and Women’s Hospital, Department of Medicine, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Boston Children’s Hospital, Informatics Program, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438) 
53  Universitätsmedizin Berlin Campus Charité Mitte, Department of Psychiatry and Psychotherapy, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662) 
54  University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, Great Britain (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
55  University Hospital of Lausanne, Institute of Social and Preventive Medicine (IUMSP), Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); Swiss Institute of Bioinformatics, Lausanne, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006) 
56  University of Edinburgh, Division of Psychiatry, Centre for Clinical Brain Sciences, Edinburgh, Great Britain (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); Mental Health, NHS 24, Glasgow, Great Britain (GRID:grid.422655.2) (ISNI:0000 0000 9506 6213) 
57  The University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
58  University of Bonn, Department of Psychiatry and Psychotherapy, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
59  University of Oxford, Statistics, Oxford, Great Britain (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
60  Columbia University College of Physicians and Surgeons, Psychiatry, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
61  The University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); Queensland University of Technology, School of Psychology and Counseling, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953) 
62  Vrije Universiteit Amsterdam, Dept of Biological Psychology & EMGO+Institute for Health and Care Research, Amsterdam, Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); Children’s Health Queensland Hospital and Health Service, Child and Youth Mental Health Service, South Brisbane, Australia (GRID:grid.12380.38); University of Queensland, Child Health Research Centre, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
63  University of Tartu, Estonian Genome Center, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) 
64  University of British Columbia, Medical Genetics, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830); University of British Columbia, Statistics, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
65  University Medicine, University Medicine Greifswald, DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany (GRID:grid.5603.0); University Medicine Greifswald, Institute of Clinical Chemistry and Laboratory Medicine, Greifswald, Germany (GRID:grid.5603.0) 
66  University of British Columbia, Statistics, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
67  Queensland University of Technology, Institute of Health and Biomedical Innovation, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953) 
68  Humus, Reykjavik, Iceland (GRID:grid.13097.3c) 
69  Virginia Commonwealth University, Department of Psychiatry, Richmond, USA (GRID:grid.224260.0) (ISNI:0000 0004 0458 8737); Virginia Commonwealth University, Virginia Institute for Psychiatric & Behavioral Genetics, Richmond, USA (GRID:grid.224260.0) (ISNI:0000 0004 0458 8737) 
70  Vrije Universiteit Medical Center, Clinical Genetics, Amsterdam, Netherlands (GRID:grid.16872.3a) (ISNI:0000 0004 0435 165X); Vrije Universiteit Amsterdam, Complex Trait Genetics, Amsterdam, Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
71  Solid Biosciences, Boston, USA (GRID:grid.12380.38) 
72  Washington University in Saint Louis School of Medicine, Department of Psychiatry, Saint Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
73  King’s College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); University of Granada, Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, Granada, Spain (GRID:grid.4489.1) (ISNI:0000000121678994) 
74  Erasmus MC, Epidemiology, Rotterdam, Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
75  University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598) 
76  Ludwig Maximilian University Munich, Department of Psychiatry and Psychotherapy, University Hospital, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X); Ludwig Maximilian University Munich, Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X) 
77  National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
78  Kaiser Permanente Washington, Behavioral Health Services, Seattle, USA (GRID:grid.488833.c) (ISNI:0000 0004 0615 7519) 
79  University of Iceland, Faculty of Medicine, Department of Psychiatry, Reykjavik, Iceland (GRID:grid.14013.37) (ISNI:0000 0004 0640 0021) 
80  James Cook University, School of Medicine and Dentistry, Townsville, Australia (GRID:grid.1011.1) (ISNI:0000 0004 0474 1797) 
81  University of Glasgow, Institute of Health and Wellbeing, Glasgow, Great Britain (GRID:grid.8756.c) (ISNI:0000 0001 2193 314X) 
82  deCODE Genetics/Amgen, Reykjavik, Iceland (GRID:grid.8756.c) 
83  Cardiff University, College of Biomedical and Life Sciences, Cardiff, Great Britain (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670) 
84  University of Münster, Institute of Epidemiology and Social Medicine, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
85  University Medicine Greifswald, Institute for Community Medicine, Greifswald, Germany (GRID:grid.5603.0) 
86  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836); University of California, San Diego, Department of Psychiatry, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242); Oslo University Hospital, KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
87  University of Edinburgh, Medical Genetics Section, CGEM, IGMM, Edinburgh, Great Britain (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
88  deCODE Genetics/Amgen, Reykjavik, Iceland (GRID:grid.4305.2) 
89  University of Cambridge, Clinical Neurosciences, Cambridge, Great Britain (GRID:grid.5335.0) (ISNI:0000000121885934) 
90  Erasmus MC, Internal Medicine, Rotterdam, Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
91  F. Hoffmann-La Roche Ltd, Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, Basel, Switzerland (GRID:grid.417570.0) (ISNI:0000 0004 0374 1269) 
92  University Medicine Greifswald, Department of Psychiatry and Psychotherapy, Greifswald, Germany (GRID:grid.5603.0) 
93  Leiden University Medical Center, Department of Psychiatry, Leiden, Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978) 
94  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836); Oslo University Hospital, KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
95  Virginia Commonwealth University, Virginia Institute for Psychiatric & Behavioral Genetics, Richmond, USA (GRID:grid.224260.0) (ISNI:0000 0004 0458 8737) 
96  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836) 
97  Pfizer Global Research and Development, Computational Sciences Center of Emphasis, Cambridge, USA (GRID:grid.410513.2) (ISNI:0000 0000 8800 7493) 
98  The University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); The University of Queensland, Institute for Molecular Bioscience; Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
99  University of Münster, Department of Psychiatry, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288) 
100  University of Münster, Department of Psychiatry, Münster, Germany (GRID:grid.5949.1) (ISNI:0000 0001 2172 9288); University of Melbourne, Department of Psychiatry, Melbourne Medical School, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); University of Melbourne, Florey Institute for Neuroscience and Mental Health, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
101  University of Bonn, School of Medicine & University Hospital Bonn, Institute of Human Genetics, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300); University of Basel, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642); University Hospital Basel, University of Basel, Institute of Medical Genetics and Pathology, Basel, Switzerland (GRID:grid.6612.3); Research Center Juelich, Institute of Neuroscience and Medicine (INM-1), Juelich, Germany (GRID:grid.8385.6) (ISNI:0000 0001 2297 375X) 
102  Vrije Universiteit Amsterdam, Dept of Biological Psychology & EMGO+Institute for Health and Care Research, Amsterdam, Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227); Vrije Universiteit Medical Center, Amsterdam Public Health Institute, Amsterdam, Netherlands (GRID:grid.16872.3a) (ISNI:0000 0004 0435 165X) 
103  Università degli Studi di Trento, Centre for Integrative Biology, Trento, Italy (GRID:grid.11696.39) (ISNI:0000 0004 1937 0351) 
104  University of Freiburg, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany (GRID:grid.5963.9); University of Freiburg, Center for NeuroModulation, Faculty of Medicine, Freiburg, Germany (GRID:grid.5963.9) 
105  Broad Institute, Medical and Population Genetics, Cambridge, USA (GRID:grid.66859.34); University of Tartu, Estonian Genome Center, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) 
106  Kaiser Permanente Northern California, Psychiatry, San Francisco, USA (GRID:grid.280062.e) (ISNI:0000 0000 9957 7758) 
107  University of Edinburgh, Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, Great Britain (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
108  Max Planck Institute of Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095); University of Toronto, Department of Psychiatry, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); Centre for Addiction and Mental Health, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925) 
109  University College London, Division of Psychiatry, London, Great Britain (GRID:grid.83440.3b) (ISNI:0000000121901201) 
110  Janssen Research and Development, LLC, Neuroscience Therapeutic Area, Titusville, USA (GRID:grid.497530.c) (ISNI:0000 0004 0389 4927) 
111  University of Tartu, Estonian Genome Center, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661); University of Tartu, Institute of Molecular and Cell Biology, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) 
112  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University Hospital, Psychosis Research Unit, Risskov, Denmark (GRID:grid.154185.c) (ISNI:0000 0004 0512 597X) 
113  Aarhus University, Centre for Integrated Register-based Research, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Aarhus University, National Centre for Register-Based Research, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Aarhus University, iSEQ, Centre for Integrative Sequencing, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
114  Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (GRID:grid.452617.3); University of Liverpool, Liverpool, Great Britain (GRID:grid.10025.36) (ISNI:0000 0004 1936 8470) 
115  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Copenhagen Universtity Hospital, Mental Health Center Copenhagen, Copenhagen, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373) 
116  Pfizer Global Research and Development, Human Genetics and Computational Biomedicine, Groton, USA (GRID:grid.410513.2) (ISNI:0000 0000 8800 7493) 
117  Massachusetts General Hospital, Department of Psychiatry, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Medical School, Psychiatry, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
118  University of Iowa, Psychiatry, Iowa City, USA (GRID:grid.214572.7) (ISNI:0000 0004 1936 8294) 
119  Heidelberg University, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Mannheim, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373); Ludwig Maximilian University Munich, Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X); Johns Hopkins University, Department of Psychiatry and Behavioral Sciences, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311); University Medical Center Göttingen, Department of Psychiatry and Psychotherapy, Goettingen, Germany (GRID:grid.411984.1) (ISNI:0000 0001 0482 5331); NIMH Division of Intramural Research Programs, Human Genetics Branch, Bethesda, USA (GRID:grid.416868.5) (ISNI:0000 0004 0464 0574) 
120  deCODE Genetics/Amgen, Reykjavik, Iceland (GRID:grid.66859.34); University of Iceland, Faculty of Medicine, Reykjavik, Iceland (GRID:grid.14013.37) (ISNI:0000 0004 0640 0021) 
121  Erasmus MC, Epidemiology, Rotterdam, Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Erasmus MC, Child and Adolescent Psychiatry, Rotterdam, Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Erasmus MC, Psychiatry, Rotterdam, Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
122  Dalhousie University, Psychiatry, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200) 
123  Columbia University College of Physicians and Surgeons, Psychiatry, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729); New York State Psychiatric Institute, Division of Epidemiology, New York, USA (GRID:grid.413734.6) (ISNI:0000 0000 8499 1112) 
124  The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (GRID:grid.452548.a) (ISNI:0000 0000 9817 5300); Mental Health Services Capital Region of Denmark, Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen, Denmark (GRID:grid.466916.a) (ISNI:0000 0004 0631 4836); University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
125  King’s College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); King’s College London, Department of Medical & Molecular Genetics, London, Great Britain (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
126  Stanford University, Psychiatry & Behavioral Sciences, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
127  King’s College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764); King’s College London, NIHR Maudsley Biomedical Research Centre, London, Great Britain (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
128  Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); University of North Carolina at Chapel Hill, Genetics, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000000122483208); University of North Carolina at Chapel Hill, Psychiatry, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000000122483208) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-16022-0
ProQuest document ID
2400097097
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.