Age at first birth in women is genetically associated with increased risk of schizophrenia
Abstract Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at fi...
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Springer Nature
2018
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Online Access: | http://urn.fi/urn:nbn:fi-fe2018111448098 |
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Abstract Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is −0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health. Consortia Schizophrenia Working Group of the Psychiatric Genomics Consortium Stephan Ripke5,6, Benjamin M. Neale5,6,7,8, Aiden Corvin9, James T. R. Walters10, Kai-How Farh5, Peter A. Holmans10,11, Phil Lee5,6,8, Brendan Bulik-Sullivan5,6, David A. Collier12,13, Hailiang Huang5,7, Tune H. Pers7,14,15, Ingrid Agartz16,17,18, Esben Agerbo19,20,21, Margot Albus22, Madeline Alexander23, Farooq Amin24,25, Silviu A. Bacanu26, Martin Begemann27, Richard A. Belliveau6, Judit Bene28,29, Sarah E. Bergen6,30, Elizabeth Bevilacqua6, Tim B. Bigdeli26, Donald W. Black31, Richard Bruggeman32, Nancy G. Buccola33, Randy L. Buckner34,35,36, William Byerley37, Wiepke Cahn38, Guiqing Cai39,40, Dominique Campion41, Rita M. Cantor42, Vaughan J. Carr43,44, Noa Carrera10, Stanley V. Catts43,45, Kimberly D. Chambert6, Raymond C. K. Chan46, Ronald Y. L. Chen47, Eric Y. H. Chen47,48, Wei Cheng49, Eric F. C. Cheung50, Siow Ann Chong51, C. Robert Cloninger52, David Cohen53, Nadine Cohen54, Paul Cormican9, Nick Craddock10,11, James J. Crowley55, David Curtis56,57, Michael Davidson58, Kenneth L. Davis40, Franziska Degenhardt59,60, Jurgen Del Favero61, Ditte Demontis21,62,63, Dimitris Dikeos64, Timothy Dinan65, Srdjan Djurovic18,66, Gary Donohoe9,67, Elodie Drapeau40, Jubao Duan68,69, Frank Dudbridge70, Naser Durmishi71, Peter Eichhammer72, Johan Eriksson73,74,75, Valentina Escott-Price10, Laurent Essioux76, Ayman H. Fanous77,78,79,80, Martilias S. Farrell55, Josef Frank81, Lude Franke82, Robert Freedman83, Nelson B. Freimer84, Marion Friedl85, Joseph I. Friedman40, Menachem Fromer5,6,8,86, Giulio Genovese6, Lyudmila Georgieva10, Ina Giegling85,87, Paola Giusti-Rodríguez55, Stephanie Godard88, Jacqueline I. Goldstein5,7, Vera Golimbet89, Srihari Gopal90, Lieuwe de Haan91, Christian Hammer27, Marian L. Hamshere10, Mark Hansen92, Thomas Hansen21,93, Vahram Haroutunian40,94,95, Annette M. Hartmann85, Frans A. Henskens43,96,97, Stefan Herms59,60,98, Joel N. Hirschhorn7,15,99, Per Hoffmann59,60,98, Andrea Hofman59,60, Mads V. Hollegaard100, David M. Hougaard100, Masashi Ikeda101, Inge Joa102, Antonio Juliá103, René S. Kahn38, Luba Kalaydjieva104,105, Sena Karachanak-Yankova106, Juha Karjalainen82, David Kavanagh10, Matthew C. Keller107, James L. Kennedy108,109,110, Andrey Khrunin111, Yunjung Kim55, Janis Klovins112, James A. Knowles113, Bettina Konte85, Vaidutis Kucinskas114, Zita Ausrele Kucinskiene114, Hana Kuzelova-Ptackova115, Anna K. Kähler30, Claudine Laurent23,116, Jimmy Lee Chee Keong51,117, Sophie E. Legge10, Bernard Lerer118, Miaoxin Li47,48,119, Tao Li120, Kung-Yee Liang121, Jeffrey Lieberman122, Svetlana Limborska111, Carmel M. Loughland43,123, Jan Lubinski124, Jouko Lönnqvist125, Milan Macek115, Patrik K. E. Magnusson30, Brion S. Maher126, Wolfgang Maier127, Jacques Mallet128, Sara Marsal103, Manuel Mattheisen21,62,63,129, Morten Mattingsdal18,130, Robert W. McCarley131,132, Colm McDonald133, Andrew M. McIntosh134,135, Sandra Meier81, Carin J. Meijer91, Bela Melegh28,29, Ingrid Melle18,136, Raquelle I. Mesholam-Gately131,137, Andres Metspalu138, Patricia T. Michie43,139, Lili Milani138, Vihra Milanova140, Younes Mokrab12, Derek W. Morris9,67, Ole Mors21,62,141, Kieran C. Murphy142, Robin M. Murray143, Inez Myin-Germeys144, Bertram Müller-Myhsok145,146,147, Mari Nelis138, Igor Nenadic148, Deborah A. Nertney149, Gerald Nestadt150, Kristin K. Nicodemus151, Liene Nikitina-Zake112, Laura Nisenbaum152, Annelie Nordin153, Eadbhard O’Callaghan154, Colm O’Dushlaine6, F. Anthony O’Neill155, Sang-Yun Oh156, Ann Olincy83, Line Olsen21,93, Jim Van Os144,157, Christos Pantelis43,158, George N. Papadimitriou64, Sergi Papiol27, Elena Parkhomenko40, Michele T. Pato113, Tiina Paunio159,160, Milica Pejovic-Milovancevic161, Diana O. Perkins162, Olli Pietiläinen160,163, Jonathan Pimm57, Andrew J. Pocklington10, John Powell143, Alkes Price7,164, Ann E. Pulver150, Shaun M. Purcell86, Digby Quested165, Henrik B. Rasmussen21,93, Abraham Reichenberg40, Mark A. Reimers166, Alexander L. Richards10, Joshua L. Roffman34,36, Panos Roussos86,167, Douglas M. Ruderfer10,86, Veikko Salomaa75, Alan R. Sanders68,69, Ulrich Schall43,123, Christian R. Schubert168, Thomas G. Schulze81,169, Sibylle G. Schwab170, Edward M. Scolnick6, Rodney J. Scott43,171,172, Larry J. Seidman131,137, Jianxin Shi173, Engilbert Sigurdsson174, Teimuraz Silagadze175, Jeremy M. Silverman40,176, Kang Sim51, Petr Slominsky111, Jordan W. Smoller6,8, Hon-Cheong So47, Chris C. A. Spencer177, Eli A. Stahl7,86, Hreinn Stefansson178, Stacy Steinberg178, Elisabeth Stogmann179, Richard E. Straub180, Eric Strengman38,181, Jana Strohmaier81, T. Scott Stroup122, Mythily Subramaniam51, Jaana Suvisaari125, Dragan M. Svrakic52, Jin P. Szatkiewicz55, Erik Söderman16, Srinivas Thirumalai182, Draga Toncheva106, Sarah Tosato183, Juha Veijola184,185, John Waddington186, Dermot Walsh187, Dai Wang90, Qiang Wang120, Bradley T. Webb26, Mark Weiser58, Dieter B. Wildenauer188, Nigel M. Williams10, Stephanie Williams55, Stephanie H. Witt81, Aaron R. Wolen166, Emily H. M. Wong47, Brandon K. Wormley26, Hualin Simon Xi189, Clement C. Zai108,109, Xuebin Zheng190, Fritz Zimprich179, Kari Stefansson178, Peter M. Visscher3, Rolf Adolfsson153, Ole A. Andreassen18,136, Douglas H. R. Blackwood135, Elvira Bramon191, Joseph D. Buxbaum39,40,94,192, Anders D. Børglum21,62,63,141, Sven Cichon59,60,98,193, Ariel Darvasi194, Enrico Domenici195, Hannelore Ehrenreich27, Tõnu Esko7,15,99,138, Pablo V. Gejman68,69, Michael Gill9, Hugh Gurling57, Christina M. Hultman30, Nakao Iwata101, Assen V. Jablensky43,105,188,196, Erik G. Jönsson16,18, Kenneth S. Kendler197, George Kirov10, Jo Knight108,109,110, Todd Lencz198,199,200, Douglas F. Levinson23, Qingqin S. Li90, Jianjun Liu190,201, Anil K. Malhotra198,199,200, Steven A. McCarroll6,99, Andrew McQuillin57, Jennifer L. Moran6, Preben B. Mortensen19,20,21, Bryan J. Mowry86,202, Markus M. Nöthen59,60, Roel A. Ophoff38,42,84, Michael J. Owen10,11, Aarno Palotie6,8,163, Carlos N. Pato113, Tracey L. Petryshen6,131,203, Danielle Posthuma204,205,206, Marcella Rietschel81, Brien P. Riley197, Dan Rujescu85,87, Pak C. 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University Medical Center Groningen, Department of Psychiatry, University of Groningen, Groningen, NL-9700, RB, The Netherlands. 33 School of Nursing, Louisiana State University Health Sciences Center, New Orleans, Louisiana, 70112, USA. 34 Athinoula A Martinos Center, Massachusetts General Hospital, Boston, Massachusetts, 02129, USA. 35 Center for Brain Science, Harvard University, Cambridge, Massachusetts, 02138, USA. 36 Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA. 37 Department of Psychiatry, University of California at San Francisco, San Francisco, California, 94143, USA. 38 University Medical Center Utrecht, Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, 3584, Utrecht, The Netherlands. 39 Department of Human Genetics, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 40 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 41 Centre Hospitalier du 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Skopje, 1000, Macedonia. 72 Department of Psychiatry, University of Regensburg, 93053, Regensburg, Germany. 73 Department of General Practice, Helsinki University Central Hospital, University of Helsinki, Po Box 20, Tukholmankatu 8 B, FI-00014, Helsinki, Finland. 74 Folkhälsan Research Center, Biomedicum Helsinki 1, Haartmaninkatu 8, FI-00290, Helsinki, Finland. 75 National Institute for Health and Welfare, PO Box 30, FI-00271, Helsinki, Finland. 76 Translational Technologies and Bioinformatics, Pharma Research and Early Development, F Hoffman-La Roche, CH-4070, Basel, Switzerland. 77 Department of Psychiatry, Georgetown University School of Medicine, Washington, DC, 20057, USA. 78 Department of Psychiatry, Keck School of Medicine of the University of Southern California, Los Angeles, California, 90033, USA. 79 Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, Virginia, 23298, USA. 80 Mental Health Service Line, Washington VA Medical Center, 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Paris, 75013, France. 89 Mental Health Research Centre, Russian Academy of Medical Sciences, 115522, Moscow, Russia. 90 Neuroscience Therapeutic Area, Janssen Research and Development, Raritan, New Jersey, 08869, USA. 91 Academic Medical Centre University of Amsterdam, Department of Psychiatry, 1105 AZ, Amsterdam, The Netherlands. 92 Illumina, La Jolla, California, California, 92122, USA. 93 Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services Copenhagen, Copenhagen, DK-4000, Denmark. 94 Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 95 J J Peters VA Medical Center, Bronx, New York, New York, 10468, USA. 96 Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle, NSW, 2308, Australia. 97 School of Electrical Engineering and Computer Science, University of Newcastle, Newcastle, NSW, 2308, Australia. 98 Division of Medical Genetics, Department of Biomedicine, University of 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Colorado, 80309, USA. 108 Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8, Canada. 109 Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada. 110 Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. 111 Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia. 112 Latvian Biomedical Research and Study Centre, Riga, LV-1067, Latvia. 113 Department of Psychiatry and Zilkha Neurogenetics Institute, Keck School of Medicine at University of Southern California, Los Angeles, California, 90089, USA. 114 Faculty of Medicine, Vilnius University, LT-01513, Vilnius, Lithuania. 115 Department of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, 150 06, Prague, Czech Republic. 116 Department of Child and Adolescent Psychiatry, Pierre and Marie Curie Faculty of Medicine, Paris, 75013, France. 117 Duke-NUS Graduate Medical School, Singapore, 169857, Singapore. 118 Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, 91120, Israel. 119 Centre for Genomic Sciences, The University of Hong Kong, Hong Kong, China. 120 Mental Health Centre and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. 121 Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, 21205, USA. 122 Department of Psychiatry, Columbia University, New York, New York, 10032, USA. 123 Translational Neuroscience and Mental Health, University of Newcastle, Newcastle, NSW2300, Australia. 124 Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, 70-453, Szczecin, Poland. 125 Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, PO BOX30, FI-00271, Helsinki, Finland. 126 Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, 21205, USA. 127 Department of Psychiatry, University of Bonn, D-53127, Bonn, Germany. 128 Centre National de la Recherche Scientifique, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Hôpital de la Pitié Salpêtrière, 75013, Paris, France. 129 Department of Genomics Mathematics, University of Bonn, D-53127, Bonn, Germany. 130 Research Unit, Sørlandet Hospital, 4604, Kristiansand, Norway. 131 Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, 02115, USA. 132 VA Boston Health Care System, Brockton, Massachusetts, 02301, USA. 133 Department of Psychiatry, National University of Ireland Galway, Co Galway, Ireland. 134 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH16 4SB, UK. 135 Division of Psychiatry, University of Edinburgh, Edinburgh, EH16 4SB, UK. 136 Division of Mental Health and Addiction, Oslo University Hospital, 0424, Oslo, Norway. 137 Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02114, USA. 138 Estonian Genome Center, University of Tartu, Tartu, 50090, Estonia. 139 School of Psychology, University of Newcastle, Newcastle, NSW, 2308, Australia. 140 First Psychiatric Clinic, Medical University, Sofia, 1431, Bulgaria. 141 Department P, Aarhus University Hospital, DK-8240, Risskov, Denmark. 142 Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland. 143 King’s College London, London, SE5 8AF, UK. 144 Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, 6229 HX, Maastricht, The Netherlands. 145 Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3BX, UK. 146 Max Planck Institute of Psychiatry, 80336, Munich, Germany. 147 Munich Cluster for SystemsNeurology (SyNergy), 80336, Munich, Germany. 148 Department of Psychiatry and Psychotherapy, Jena University Hospital, 07743, Jena, Germany. 149 Department of Psychiatry, Queensland Brain Institute and Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, St Lucia QLD, 4072, Australia. 150 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA. 151 Department of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. 152 Eli Lilly and Company, Lilly Corporate Center, Indianapolis, 46285, Indiana, USA. 153 Department of Clinical Sciences, Psychiatry, Umeå University, SE-901 87, Umeå, Sweden. 154 DETECT Early Intervention Service for Psychosis, Blackrock, Co Dublin, Ireland. 155 Centre for Public Health, Institute of Clinical Sciences, Queen’s University Belfast, Belfast, BT12 6AB, UK. 156 Lawrence Berkeley National Laboratory, University of California at Berkeley, Berkeley, California, 94720, USA. 157 Institute of Psychiatry, Kings College London, London, SE5 8AF, UK. 158 Melbourne Neuropsychiatry Centre, University of Melbourne & Melbourne Health, Melbourne, Vic, 3053, Australia. 159 Department of Psychiatry, University of Helsinki, PO Box 590, FI-00029, HUS, Helsinki, Finland. 160 Public Health Genomics Unit, National Institute for Health and Welfare, PO BOX 30, FI-00271, Helsinki, Finland. 161 Medical Faculty, University of Belgrade, 11000, Belgrade, Serbia. 162 Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina, 27599-7160, USA. 163 Institute for Molecular Medicine Finland, FIMM, University of Helsinki, PO Box 20, FI-00014, Helsinki, Finland. 164 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, 02115, USA. 165 Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK. 166 Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, 23298, USA. 167 Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 168 PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, 02139, USA. 169 Department of Psychiatry and Psychotherapy, University of Gottingen, 37073, Göttingen, Germany. 170 Psychiatry and Psychotherapy Clinic, University of Erlangen, 91054, Erlangen, Germany. 171 Hunter New England Health Service, Newcastle, NSW, 2308, Australia. 172 School of Biomedical Sciences, University of Newcastle, Newcastle, NSW, 2308, Australia. 173 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, 20892, USA. 174 University of Iceland, Landspitali, National University Hospital, 101, Reykjavik, Iceland. 175 Department of Psychiatry and Drug Addiction, Tbilisi State Medical University (TSMU), N33, 0177, Tbilisi, Georgia. 176 Research and Development, Bronx Veterans Affairs Medical Center, New York, New York, 10468, USA. 177 Wellcome Trust Centre for Human Genetics, Oxford, OX3 7BN, UK. 178 deCODE Genetics, 101, Reykjavik, Iceland. 179 Department of Clinical Neurology, Medical University of Vienna, 1090, Wien, Austria. 180 Lieber Institute for Brain Development, Baltimore, Maryland, 21205, USA. 181 Department of Medical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. 182 Berkshire Healthcare NHS Foundation Trust, Bracknell, RG12 1BQ, UK. 183 Section of Psychiatry, University of Verona, 37134, Verona, Italy. 184 Department of Psychiatry, University of Oulu, PO Box 5000, Oulu, 90014, Finland. 185 University Hospital of Oulu, PO Box 20, 90029, OYS, Oulu, Finland. 186 Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland. 187 Health Research Board, Dublin 2, Ireland. 188 School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA6009, Australia. 189 Computational Sciences CoE, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, 02139, USA. 190 Human Genetics, Genome Institute of Singapore, A STAR, Singapore, 138672, Singapore. 191 University College London, London, WC1E 6BT, UK. 192 Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 193 Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, 52428, Juelich, Germany. 194 Department of Genetics, The Hebrew University of Jerusalem, 91905, Jerusalem, Israel. 195 Neuroscience Discovery and Translational Area, Pharma Research and Early Development, F Hoffman-La Roche, CH-4070, Basel, Switzerland. 196 Centre for Clinical Research in Neuropsychiatry, School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Medical Research Foundation Building, Perth, WA6000, Australia. 197 Virginia Institute for Psychiatric and Behavioral Genetics, Departments of Psychiatry and Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, 23298, USA. 198 The Feinstein Institute for Medical Research, Manhasset, New York, 11030, USA. 199 The Hofstra NS-LIJ School of Medicine, Hempstead, New York, 11549, USA. 200 The Zucker Hillside Hospital, Glen Oaks, New York, 11004, USA. 201 Saw Swee Hock School of Public Health, National University of Singapore, Singapore, 117597, Singapore. 202 Queensland Centre for Mental Health Research, University of Queensland, Brisbane, 4076, Queensland, Australia. 203 Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA. 204 Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam, 3000, The Netherlands. 205 Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, Amsterdam, 1081, The Netherlands. 206 Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, 1081, The Netherlands. 207 University of Aberdeen, Institute of Medical Sciences, Aberdeen, AB25 2ZD, UK. 208 Departments of Psychiatry, Neurology, Neuroscience and Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, 21205, USA. 209 Department of Clinical Medicine, University of Copenhagen, Copenhagen, 2200, Denmark. |
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Ni, G. (Guiyan) Gratten, J. (Jacob) Wray, N. R. (Naomi R.) Lee, S. H. (Sang Hong) S. W. (Schizophrenia Working Group of the Psychiatric Genomics Consortium) |
spellingShingle |
Ni, G. (Guiyan) Gratten, J. (Jacob) Wray, N. R. (Naomi R.) Lee, S. H. (Sang Hong) S. W. (Schizophrenia Working Group of the Psychiatric Genomics Consortium) Age at first birth in women is genetically associated with increased risk of schizophrenia |
author_facet |
Ni, G. (Guiyan) Gratten, J. (Jacob) Wray, N. R. (Naomi R.) Lee, S. H. (Sang Hong) S. W. (Schizophrenia Working Group of the Psychiatric Genomics Consortium) |
author_sort |
Ni, G. (Guiyan) |
title |
Age at first birth in women is genetically associated with increased risk of schizophrenia |
title_short |
Age at first birth in women is genetically associated with increased risk of schizophrenia |
title_full |
Age at first birth in women is genetically associated with increased risk of schizophrenia |
title_fullStr |
Age at first birth in women is genetically associated with increased risk of schizophrenia |
title_full_unstemmed |
Age at first birth in women is genetically associated with increased risk of schizophrenia |
title_sort |
age at first birth in women is genetically associated with increased risk of schizophrenia |
publisher |
Springer Nature |
publishDate |
2018 |
url |
http://urn.fi/urn:nbn:fi-fe2018111448098 |
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Brisbane Brockton Canada Castle Peak Chapel Hill Ditte Draga Jebsen Jeremy Kari Kung Marian Norway Olli Orleans Pablo Queensland Rouen SalpÊtriÈre St. Louis Stacy Sven Sørlandet Tbilisi Todd Valentina |
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Brisbane Brockton Canada Castle Peak Chapel Hill Ditte Draga Jebsen Jeremy Kari Kung Marian Norway Olli Orleans Pablo Queensland Rouen SalpÊtriÈre St. Louis Stacy Sven Sørlandet Tbilisi Todd Valentina |
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info:eu-repo/semantics/openAccess © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. https://creativecommons.org/licenses/by/4.0/ |
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ftunivoulu:oai:oulu.fi:nbnfi-fe2018111448098 2023-05-15T16:53:31+02:00 Age at first birth in women is genetically associated with increased risk of schizophrenia Ni, G. (Guiyan) Gratten, J. (Jacob) Wray, N. R. (Naomi R.) Lee, S. H. (Sang Hong) S. W. (Schizophrenia Working Group of the Psychiatric Genomics Consortium) 2018 application/pdf http://urn.fi/urn:nbn:fi-fe2018111448098 eng eng Springer Nature info:eu-repo/semantics/altIdentifier/eissn/2045-2322 info:eu-repo/semantics/altIdentifier/url/https://static-content.springer.com/esm/art%3A10.1038%2Fs41598-018-28160-z/MediaObjects/41598_2018_28160_MOESM1_ESM.pdf info:eu-repo/semantics/openAccess © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. https://creativecommons.org/licenses/by/4.0/ CC-BY info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2018 ftunivoulu 2021-06-25T17:54:07Z Abstract Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is −0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health. Consortia Schizophrenia Working Group of the Psychiatric Genomics Consortium Stephan Ripke5,6, Benjamin M. Neale5,6,7,8, Aiden Corvin9, James T. R. Walters10, Kai-How Farh5, Peter A. Holmans10,11, Phil Lee5,6,8, Brendan Bulik-Sullivan5,6, David A. Collier12,13, Hailiang Huang5,7, Tune H. Pers7,14,15, Ingrid Agartz16,17,18, Esben Agerbo19,20,21, Margot Albus22, Madeline Alexander23, Farooq Amin24,25, Silviu A. Bacanu26, Martin Begemann27, Richard A. Belliveau6, Judit Bene28,29, Sarah E. Bergen6,30, Elizabeth Bevilacqua6, Tim B. Bigdeli26, Donald W. Black31, Richard Bruggeman32, Nancy G. Buccola33, Randy L. Buckner34,35,36, William Byerley37, Wiepke Cahn38, Guiqing Cai39,40, Dominique Campion41, Rita M. Cantor42, Vaughan J. Carr43,44, Noa Carrera10, Stanley V. Catts43,45, Kimberly D. Chambert6, Raymond C. K. Chan46, Ronald Y. L. Chen47, Eric Y. H. Chen47,48, Wei Cheng49, Eric F. C. Cheung50, Siow Ann Chong51, C. Robert Cloninger52, David Cohen53, Nadine Cohen54, Paul Cormican9, Nick Craddock10,11, James J. Crowley55, David Curtis56,57, Michael Davidson58, Kenneth L. Davis40, Franziska Degenhardt59,60, Jurgen Del Favero61, Ditte Demontis21,62,63, Dimitris Dikeos64, Timothy Dinan65, Srdjan Djurovic18,66, Gary Donohoe9,67, Elodie Drapeau40, Jubao Duan68,69, Frank Dudbridge70, Naser Durmishi71, Peter Eichhammer72, Johan Eriksson73,74,75, Valentina Escott-Price10, Laurent Essioux76, Ayman H. Fanous77,78,79,80, Martilias S. Farrell55, Josef Frank81, Lude Franke82, Robert Freedman83, Nelson B. Freimer84, Marion Friedl85, Joseph I. Friedman40, Menachem Fromer5,6,8,86, Giulio Genovese6, Lyudmila Georgieva10, Ina Giegling85,87, Paola Giusti-Rodríguez55, Stephanie Godard88, Jacqueline I. Goldstein5,7, Vera Golimbet89, Srihari Gopal90, Lieuwe de Haan91, Christian Hammer27, Marian L. Hamshere10, Mark Hansen92, Thomas Hansen21,93, Vahram Haroutunian40,94,95, Annette M. Hartmann85, Frans A. Henskens43,96,97, Stefan Herms59,60,98, Joel N. Hirschhorn7,15,99, Per Hoffmann59,60,98, Andrea Hofman59,60, Mads V. Hollegaard100, David M. Hougaard100, Masashi Ikeda101, Inge Joa102, Antonio Juliá103, René S. Kahn38, Luba Kalaydjieva104,105, Sena Karachanak-Yankova106, Juha Karjalainen82, David Kavanagh10, Matthew C. Keller107, James L. Kennedy108,109,110, Andrey Khrunin111, Yunjung Kim55, Janis Klovins112, James A. Knowles113, Bettina Konte85, Vaidutis Kucinskas114, Zita Ausrele Kucinskiene114, Hana Kuzelova-Ptackova115, Anna K. Kähler30, Claudine Laurent23,116, Jimmy Lee Chee Keong51,117, Sophie E. Legge10, Bernard Lerer118, Miaoxin Li47,48,119, Tao Li120, Kung-Yee Liang121, Jeffrey Lieberman122, Svetlana Limborska111, Carmel M. Loughland43,123, Jan Lubinski124, Jouko Lönnqvist125, Milan Macek115, Patrik K. E. Magnusson30, Brion S. Maher126, Wolfgang Maier127, Jacques Mallet128, Sara Marsal103, Manuel Mattheisen21,62,63,129, Morten Mattingsdal18,130, Robert W. McCarley131,132, Colm McDonald133, Andrew M. McIntosh134,135, Sandra Meier81, Carin J. Meijer91, Bela Melegh28,29, Ingrid Melle18,136, Raquelle I. Mesholam-Gately131,137, Andres Metspalu138, Patricia T. Michie43,139, Lili Milani138, Vihra Milanova140, Younes Mokrab12, Derek W. Morris9,67, Ole Mors21,62,141, Kieran C. Murphy142, Robin M. Murray143, Inez Myin-Germeys144, Bertram Müller-Myhsok145,146,147, Mari Nelis138, Igor Nenadic148, Deborah A. Nertney149, Gerald Nestadt150, Kristin K. Nicodemus151, Liene Nikitina-Zake112, Laura Nisenbaum152, Annelie Nordin153, Eadbhard O’Callaghan154, Colm O’Dushlaine6, F. Anthony O’Neill155, Sang-Yun Oh156, Ann Olincy83, Line Olsen21,93, Jim Van Os144,157, Christos Pantelis43,158, George N. Papadimitriou64, Sergi Papiol27, Elena Parkhomenko40, Michele T. Pato113, Tiina Paunio159,160, Milica Pejovic-Milovancevic161, Diana O. Perkins162, Olli Pietiläinen160,163, Jonathan Pimm57, Andrew J. Pocklington10, John Powell143, Alkes Price7,164, Ann E. Pulver150, Shaun M. Purcell86, Digby Quested165, Henrik B. Rasmussen21,93, Abraham Reichenberg40, Mark A. Reimers166, Alexander L. Richards10, Joshua L. Roffman34,36, Panos Roussos86,167, Douglas M. Ruderfer10,86, Veikko Salomaa75, Alan R. Sanders68,69, Ulrich Schall43,123, Christian R. Schubert168, Thomas G. Schulze81,169, Sibylle G. Schwab170, Edward M. Scolnick6, Rodney J. Scott43,171,172, Larry J. Seidman131,137, Jianxin Shi173, Engilbert Sigurdsson174, Teimuraz Silagadze175, Jeremy M. Silverman40,176, Kang Sim51, Petr Slominsky111, Jordan W. Smoller6,8, Hon-Cheong So47, Chris C. A. Spencer177, Eli A. Stahl7,86, Hreinn Stefansson178, Stacy Steinberg178, Elisabeth Stogmann179, Richard E. Straub180, Eric Strengman38,181, Jana Strohmaier81, T. Scott Stroup122, Mythily Subramaniam51, Jaana Suvisaari125, Dragan M. Svrakic52, Jin P. Szatkiewicz55, Erik Söderman16, Srinivas Thirumalai182, Draga Toncheva106, Sarah Tosato183, Juha Veijola184,185, John Waddington186, Dermot Walsh187, Dai Wang90, Qiang Wang120, Bradley T. Webb26, Mark Weiser58, Dieter B. Wildenauer188, Nigel M. Williams10, Stephanie Williams55, Stephanie H. Witt81, Aaron R. 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University Medical Center Groningen, Department of Psychiatry, University of Groningen, Groningen, NL-9700, RB, The Netherlands. 33 School of Nursing, Louisiana State University Health Sciences Center, New Orleans, Louisiana, 70112, USA. 34 Athinoula A Martinos Center, Massachusetts General Hospital, Boston, Massachusetts, 02129, USA. 35 Center for Brain Science, Harvard University, Cambridge, Massachusetts, 02138, USA. 36 Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA. 37 Department of Psychiatry, University of California at San Francisco, San Francisco, California, 94143, USA. 38 University Medical Center Utrecht, Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, 3584, Utrecht, The Netherlands. 39 Department of Human Genetics, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 40 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 41 Centre Hospitalier du Rouvray and INSERM U1079 Faculty of Medicine, 76301, Rouen, France. 42 Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California, 90095, USA. 43 Schizophrenia Research Institute, Sydney, NSW, 2010, Australia. 44 School of Psychiatry, University of New South Wales, Sydney, NSW, 2031, Australia. 45 Royal Brisbane and Women’s Hospital, University of Queensland, Brisbane, St Lucia, QLD, 4072, Australia. 46 Institute of Psychology, Chinese Academy of Science, Beijing, 100101, China. 47 Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 48 State Key Laboratory for Brain and Cognitive Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 49 Department of Computer Science, University of North Carolina, Chapel Hill, North Carolina, 27514, USA. 50 Castle Peak Hospital, Hong Kong, China. 51 Institute of Mental Health, Singapore, 539747, Singapore. 52 Department of Psychiatry, Washington University, St. Louis, Missouri, 63110, USA. 53 Department of Child and Adolescent Psychiatry, Assistance Publique Hopitaux de Paris, Pierre and Marie Curie Faculty of Medicine and Institute for Intelligent Systems and Robotics, Paris, 75013, France. 54 Blue Note Biosciences, Princeton, New Jersey, 08540, USA. 55 Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, 27599-7264, USA. 56 Department of Psychological Medicine, Queen Mary University of London, London, E1 1BB, UK. 57 Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London, WC1E6JJ, UK. 58 Sheba Medical Center, Tel Hashomer, 52621, Israel. 59 Department of Genomics, Life and Brain Center, D-53127, Bonn, Germany. 60 Institute of Human Genetics, University of Bonn, D-53127, Bonn, Germany. 61 Applied Molecular Genomics Unit, VIB Department of Molecular Genetics, University of Antwerp, B-2610, Antwerp, Belgium. 62 Centre for 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Skopje, 1000, Macedonia. 72 Department of Psychiatry, University of Regensburg, 93053, Regensburg, Germany. 73 Department of General Practice, Helsinki University Central Hospital, University of Helsinki, Po Box 20, Tukholmankatu 8 B, FI-00014, Helsinki, Finland. 74 Folkhälsan Research Center, Biomedicum Helsinki 1, Haartmaninkatu 8, FI-00290, Helsinki, Finland. 75 National Institute for Health and Welfare, PO Box 30, FI-00271, Helsinki, Finland. 76 Translational Technologies and Bioinformatics, Pharma Research and Early Development, F Hoffman-La Roche, CH-4070, Basel, Switzerland. 77 Department of Psychiatry, Georgetown University School of Medicine, Washington, DC, 20057, USA. 78 Department of Psychiatry, Keck School of Medicine of the University of Southern California, Los Angeles, California, 90033, USA. 79 Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, Virginia, 23298, USA. 80 Mental Health Service Line, Washington VA Medical Center, Washington, DC, 20422, USA. 81 Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, D-68159, Mannheim, Germany. 82 Department of Genetics, University of Groningen, University Medical Centre Groningen, 9700 RB, Groningen, The Netherlands. 83 Department of Psychiatry, University of Colorado Denver, Aurora, Colorado, 80045, USA. 84 Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California, 90095, USA. 85 Department of Psychiatry, University of Halle, 06112, Halle, Germany. 86 Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, New York, 10029, USA. 87 Department of Psychiatry, University of Munich, 80336, Munich, Germany. 88 Departments of Psychiatry and Human and Molecular Genetics, INSERM, Institut de Myologie, Hôpital de la Pitiè-Salpêtrière, Paris, 75013, France. 89 Mental Health Research Centre, Russian Academy of Medical Sciences, 115522, Moscow, Russia. 90 Neuroscience Therapeutic Area, Janssen Research and Development, Raritan, New Jersey, 08869, USA. 91 Academic Medical Centre University of Amsterdam, Department of Psychiatry, 1105 AZ, Amsterdam, The Netherlands. 92 Illumina, La Jolla, California, California, 92122, USA. 93 Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services Copenhagen, Copenhagen, DK-4000, Denmark. 94 Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 95 J J Peters VA Medical Center, Bronx, New York, New York, 10468, USA. 96 Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle, NSW, 2308, Australia. 97 School of Electrical Engineering and Computer Science, University of Newcastle, Newcastle, NSW, 2308, Australia. 98 Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, CH-4058, Switzerland. 99 Department of Genetics, Harvard Medical School, Boston, Massachusetts, Massachusetts, 02115, USA. 100 Section of Neonatal Screening and Hormones, Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, DK-2300, Denmark. 101 Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan. 102 Regional Centre for Clinical Research in Psychosis, Department of Psychiatry, Stavanger University Hospital, 4011, Stavanger, Norway. 103 Rheumatology Research Group, Vall d’Hebron Research Institute, Barcelona, 08035, Spain. 104 Centre for Medical Research, The University of Western Australia, Perth, WA6009, Australia. 105 The Perkins Institute for Medical Research, The University of Western Australia, Perth, WA6009, Australia. 106 Department of Medical Genetics, Medical University, Sofia, 1431, Bulgaria. 107 Department of Psychology, University of Colorado Boulder, Boulder, Colorado, 80309, USA. 108 Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R8, Canada. 109 Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T 1R8, Canada. 110 Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. 111 Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia. 112 Latvian Biomedical Research and Study Centre, Riga, LV-1067, Latvia. 113 Department of Psychiatry and Zilkha Neurogenetics Institute, Keck School of Medicine at University of Southern California, Los Angeles, California, 90089, USA. 114 Faculty of Medicine, Vilnius University, LT-01513, Vilnius, Lithuania. 115 Department of Biology and Medical Genetics, 2nd Faculty of Medicine and University Hospital Motol, 150 06, Prague, Czech Republic. 116 Department of Child and Adolescent Psychiatry, Pierre and Marie Curie Faculty of Medicine, Paris, 75013, France. 117 Duke-NUS Graduate Medical School, Singapore, 169857, Singapore. 118 Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, 91120, Israel. 119 Centre for Genomic Sciences, The University of Hong Kong, Hong Kong, China. 120 Mental Health Centre and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. 121 Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, 21205, USA. 122 Department of Psychiatry, Columbia University, New York, New York, 10032, USA. 123 Translational Neuroscience and Mental Health, University of Newcastle, Newcastle, NSW2300, Australia. 124 Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, 70-453, Szczecin, Poland. 125 Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, PO BOX30, FI-00271, Helsinki, Finland. 126 Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, 21205, USA. 127 Department of Psychiatry, University of Bonn, D-53127, Bonn, Germany. 128 Centre National de la Recherche Scientifique, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs, Hôpital de la Pitié Salpêtrière, 75013, Paris, France. 129 Department of Genomics Mathematics, University of Bonn, D-53127, Bonn, Germany. 130 Research Unit, Sørlandet Hospital, 4604, Kristiansand, Norway. 131 Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, 02115, USA. 132 VA Boston Health Care System, Brockton, Massachusetts, 02301, USA. 133 Department of Psychiatry, National University of Ireland Galway, Co Galway, Ireland. 134 Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH16 4SB, UK. 135 Division of Psychiatry, University of Edinburgh, Edinburgh, EH16 4SB, UK. 136 Division of Mental Health and Addiction, Oslo University Hospital, 0424, Oslo, Norway. 137 Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02114, USA. 138 Estonian Genome Center, University of Tartu, Tartu, 50090, Estonia. 139 School of Psychology, University of Newcastle, Newcastle, NSW, 2308, Australia. 140 First Psychiatric Clinic, Medical University, Sofia, 1431, Bulgaria. 141 Department P, Aarhus University Hospital, DK-8240, Risskov, Denmark. 142 Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin 2, Ireland. 143 King’s College London, London, SE5 8AF, UK. 144 Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, 6229 HX, Maastricht, The Netherlands. 145 Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3BX, UK. 146 Max Planck Institute of Psychiatry, 80336, Munich, Germany. 147 Munich Cluster for SystemsNeurology (SyNergy), 80336, Munich, Germany. 148 Department of Psychiatry and Psychotherapy, Jena University Hospital, 07743, Jena, Germany. 149 Department of Psychiatry, Queensland Brain Institute and Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, St Lucia QLD, 4072, Australia. 150 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA. 151 Department of Psychiatry, Trinity College Dublin, Dublin 2, Ireland. 152 Eli Lilly and Company, Lilly Corporate Center, Indianapolis, 46285, Indiana, USA. 153 Department of Clinical Sciences, Psychiatry, Umeå University, SE-901 87, Umeå, Sweden. 154 DETECT Early Intervention Service for Psychosis, Blackrock, Co Dublin, Ireland. 155 Centre for Public Health, Institute of Clinical Sciences, Queen’s University Belfast, Belfast, BT12 6AB, UK. 156 Lawrence Berkeley National Laboratory, University of California at Berkeley, Berkeley, California, 94720, USA. 157 Institute of Psychiatry, Kings College London, London, SE5 8AF, UK. 158 Melbourne Neuropsychiatry Centre, University of Melbourne & Melbourne Health, Melbourne, Vic, 3053, Australia. 159 Department of Psychiatry, University of Helsinki, PO Box 590, FI-00029, HUS, Helsinki, Finland. 160 Public Health Genomics Unit, National Institute for Health and Welfare, PO BOX 30, FI-00271, Helsinki, Finland. 161 Medical Faculty, University of Belgrade, 11000, Belgrade, Serbia. 162 Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina, 27599-7160, USA. 163 Institute for Molecular Medicine Finland, FIMM, University of Helsinki, PO Box 20, FI-00014, Helsinki, Finland. 164 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, 02115, USA. 165 Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK. 166 Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, 23298, USA. 167 Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 168 PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, 02139, USA. 169 Department of Psychiatry and Psychotherapy, University of Gottingen, 37073, Göttingen, Germany. 170 Psychiatry and Psychotherapy Clinic, University of Erlangen, 91054, Erlangen, Germany. 171 Hunter New England Health Service, Newcastle, NSW, 2308, Australia. 172 School of Biomedical Sciences, University of Newcastle, Newcastle, NSW, 2308, Australia. 173 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, 20892, USA. 174 University of Iceland, Landspitali, National University Hospital, 101, Reykjavik, Iceland. 175 Department of Psychiatry and Drug Addiction, Tbilisi State Medical University (TSMU), N33, 0177, Tbilisi, Georgia. 176 Research and Development, Bronx Veterans Affairs Medical Center, New York, New York, 10468, USA. 177 Wellcome Trust Centre for Human Genetics, Oxford, OX3 7BN, UK. 178 deCODE Genetics, 101, Reykjavik, Iceland. 179 Department of Clinical Neurology, Medical University of Vienna, 1090, Wien, Austria. 180 Lieber Institute for Brain Development, Baltimore, Maryland, 21205, USA. 181 Department of Medical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. 182 Berkshire Healthcare NHS Foundation Trust, Bracknell, RG12 1BQ, UK. 183 Section of Psychiatry, University of Verona, 37134, Verona, Italy. 184 Department of Psychiatry, University of Oulu, PO Box 5000, Oulu, 90014, Finland. 185 University Hospital of Oulu, PO Box 20, 90029, OYS, Oulu, Finland. 186 Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland. 187 Health Research Board, Dublin 2, Ireland. 188 School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA6009, Australia. 189 Computational Sciences CoE, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, 02139, USA. 190 Human Genetics, Genome Institute of Singapore, A STAR, Singapore, 138672, Singapore. 191 University College London, London, WC1E 6BT, UK. 192 Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA. 193 Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, 52428, Juelich, Germany. 194 Department of Genetics, The Hebrew University of Jerusalem, 91905, Jerusalem, Israel. 195 Neuroscience Discovery and Translational Area, Pharma Research and Early Development, F Hoffman-La Roche, CH-4070, Basel, Switzerland. 196 Centre for Clinical Research in Neuropsychiatry, School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Medical Research Foundation Building, Perth, WA6000, Australia. 197 Virginia Institute for Psychiatric and Behavioral Genetics, Departments of Psychiatry and Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia, 23298, USA. 198 The Feinstein Institute for Medical Research, Manhasset, New York, 11030, USA. 199 The Hofstra NS-LIJ School of Medicine, Hempstead, New York, 11549, USA. 200 The Zucker Hillside Hospital, Glen Oaks, New York, 11004, USA. 201 Saw Swee Hock School of Public Health, National University of Singapore, Singapore, 117597, Singapore. 202 Queensland Centre for Mental Health Research, University of Queensland, Brisbane, 4076, Queensland, Australia. 203 Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA. 204 Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam, 3000, The Netherlands. 205 Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, Amsterdam, 1081, The Netherlands. 206 Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, 1081, The Netherlands. 207 University of Aberdeen, Institute of Medical Sciences, Aberdeen, AB25 2ZD, UK. 208 Departments of Psychiatry, Neurology, Neuroscience and Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, 21205, USA. 209 Department of Clinical Medicine, University of Copenhagen, Copenhagen, 2200, Denmark. 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