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Funding Information: The authors thank all participants, clinicians and researchers for making this study possible. This CRESTAR project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement #279227. M.P. wishes to thank the MRC Centre for Drug Safety Science (grant code MR/L006758/1) for support. A.F.P. acknowledges support by a "Springboard" award (ref: SBF005 \1083) from the Academy of Medical Sciences. J.T.R.W. and M.C.O. acknowledge support by a collaborative research grant from Takeda (Takeda played no part in the conception, design, implementation or interpretation of this study). Genome-wide data of CIAC used for identifying overlapping individuals were obtained from NIMH Repository & Genomics Resource, a centralized national biorepository for genetic studies of psychiatric disorders (www.nimhgenetics. org). The collection of data and biomaterials for this study was supported by funding provided by R01 MH080403 (PIs: P.F.S., Edwin J.C.G. van den Oord) from the US National Institute of Mental Health via the American Recovery and Reinvestment Act of 2009. Dr. Denis Fourches and Dr. Alexander Tropsha acknowledge the support from National Science Foundation grant ABI 10-567. The study was led by P.F.S., L. Fredrik Jarskog, Jeffrey A. Lieberman, J.L.K. and Mark J. Daly. Dr. Thomas Lehner (NIMH) and Dr. David Goldstein (Duke University) were also involved in assisting with this project. The authors acknowledge the assistance of Dr. Michael Karukin (Teva Pharmaceuticals) and Dr. Rafael Muniz and Dr. Vinod Kumar (Novartis) for help in accessing US national clozapine registries. Dr. Stanton Gerson (Department of Hematology, Case Western Reserve), Dr. Armond Goldman (Department of Immunology, University of Texas Galveston) and Dr. Nancy Berliner (Department of Hematology, Harvard University) provided input on mechanisms of agranulocytosis. Publisher Copyright: © 2021, The Author(s). ; The atypical antipsychotic ...

This work was supported by Medical Research Council Centre grant MR/ L010305/1, Medical Research Council Program grant MR/P005748/1, and Medical Research Council Project grants MR/L011794/1 and MC_PC_17212 to Cardiff University and by the National Centre for Mental Health, funded by the Welsh Government through Health and Care Research Wales. This work acknowledges the support of the Supercomputing Wales project, which is partially funded by the European Regional Development Fund via the Welsh Government. Dr Pardiñas was supported by an Academy of Medical Sciences Springboard Award (SBF005\1083). Dr Andreassen was supported by the Research Council of Norway (grants 283798, 262656, 248980, 273291, 248828, 248778, and 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, and the European Union's Horizon 2020 Research and Innovation Programme (grant 847776). Dr Ajnakina was supported by an National Institute for Health Research postdoctoral fellowship (PDF-2018-11-ST2-020). Dr Joyce was supported by the University College London Hospitals/UCL University College London Biomedical Research Centre. Dr Kowalec received funding from the European Union's Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement (793530) from the government of Canada Banting postdoctoral fellowship programme and the University of Manitoba. Dr Sullivan was supported by the Swedish Research Council (Vetenskapsrådet, D0886501), the European Union's Horizon 2020 programme (COSYN, 610307) and the US National Institute of Mental Health (U01 MH109528 and R01 MH077139). The Psychiatric Genomics Consortium was partly supported by the National Institute Of Mental Health (grants R01MH124873). The Sweden Schizophrenia Study was supported by the National Institute Of Mental Health (grant R01MH077139). The STRATA consortium was supported by a Stratified Medicine Programme grant to Dr MacCabe from the Medical Research Council (grant MR/L011794/1), which funded the research and supported Drs Pardiñas, ...

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files ; Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population. ; European Union's Seventh Framework Programme Medical Research Council (MRC) Centre European Community's Seventh Framework Programme German Research Foundation (DFG) Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Munster National Health and Medical Research Council (NHMRC) Agencia Estatal de Investigacion (AEI) Xunta de Galicia Fondo Europeo de Desarrollo Regional (FEDER) Lundbeck Foundation Stanley Medical Research Institute, an advanced grant from the European Research Council Danish Strategic Research Council Aarhus University Wellcome Trust Juvenile Diabetes Research Foundation (JDRF) European Union National Institute for Health Research (NIHR) programme Chief Scientist Office of the Scottish government Health Directorates Scottish Funding Council National Institute of ...