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WFSBP Consensus Paper

Genetics of schizophrenia: A consensus paper of the WFSBP Task Force on Genetics

Ina GieglingDepartment of Psychiatry, Psychotherapy, and Psychosomatics, Martin Luther University of Halle-Wittenberg, Halle, Germany; ;Department of Psychiatry, Ludwig-Maximilians-University Munich, Munich, Germany;

http://orcid.org/0000-0001-8407-7512

Ladislav HosakDepartment of Psychiatriy, Charles University, Faculty of Medicine and University Hospital in Hradec Králové, Prague, Czech Republic;

Rainald MössnerDepartment of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany;

Alessandro SerrettiDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy;

http://orcid.org/0000-0003-4363-3759

Frank BellivierFondation Fondamental, Créteil, France AP-HP, GH Saint-Louis-Lariboisière-Fernand-Widal, Pôle Neurosciences, Paris, France; ;Equipe 1, Université Paris Diderot, Paris, France;

Stephan ClaesGRASP-Research Group, Department of Neuroscience, University of Leuven, Leuven, Belgium; ;Department of Neurosciences, University Psychiatric Center KU Leuven, Leuven, Belgium;

David A. CollierSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK; ;Eli Lilly and Company Ltd, Erl Wood Manor, Surrey, UK;

http://orcid.org/0000-0003-4087-1559

Alejo CorralesArgentinean Association of Biological Psychiatry, National University, UNT, Buenos Aires, Argentina;

Lynn E. DeLisiVA Boston Health Care System, Brockton, MA, USA; ;Department of Psychiatry, Harvard Medical School, Boston, MA, USA;

Carla GalloDepartamento de Ciencias Celulares y Moleculares, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru;

Michael GillNeuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland;

James L. KennedyNeurogenetics Section, Centre for Addiction and Mental Health, Toronto, ON, Canada; ;Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada; ;Department of Psychiatry, University of Toronto, Toronto, ON, Canada; ;Collaborative Program in Neuroscience, Institute of Medical Science, University of Toronto, Toronto, ON, Canada;

http://orcid.org/0000-0002-8733-3806

Marion LeboyerEquipe Psychiatrie Translationnelle, Faculté de Médecine, Université Paris-Est Créteil, Inserm U955, Créteil, France; ;DHU Pe-Psy, Pôle de Psychiatrie et d'Addictologie, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; ;Pôle de Psychiatrie, Hôpital Albert Chenevier, Créteil, France; ;Fondation FondaMental, Créteil, France;

Wolfgang MaierDepartment of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany;

Miguel MarquezAsistencia, Docencia e Investigación en Neurociencia, Buenos Aires, Argentina;

Isabelle MassatUNI - ULB Neurosciences Institute, ULB, Bruxelles, Belgium; ;National Fund of Scientific Research (FNRS), Bruxelles, Belgium; ;Laboratory of Experimental Neurology, ULB, Bruxelles, Belgium; ;UR2NF - Neuropsychology and Functional Neuroimaging Research Unit, Centre de Recherche Cognition et Neurosciences, Université Libre de Bruxelles (ULB), Bruxelles, Belgium;

Ole MorsPsychosis Research Unit, Aarhus University Hospital, Risskov, Denmark; ;The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark;

Pierandrea MugliaUCB Biopharma, Brussels, Belgium;

Markus M. NöthenHead, Institute of Human Genetics, University of Bonn, Bonn, Germany; ;Department of Genomics, Life and Brain Center, Bonn, Germany;

Jorge Ospina-DuqueGrupo de Investigación en Psiquiatría, Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia;

Michael J. OwenMRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK; ;National Centre for Mental Health, Cardiff University, Cardiff, UK;

Peter ProppingUniversity of Bonn, Bonn, Germany;

YongYong ShiBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China; ;Shandong Provincial Key Laboratory of Metabloic Disease, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China; ;Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, P.R. China;

David St ClairDepartment of Psychiatry, University of Aberdeen, Institute of Medical Sciences, Aberdeen, UK;

Florence ThibautINSERM U 894 Centre Psychiatry and Neurosciences, University Hospital Cochin (Site Tarnier), University Sorbonne Paris Cité (Faculty of Medicine Paris Descartes), Paris, France;

http://orcid.org/0000-0002-0204-5435

Sven CichonHead, Institute of Human Genetics, University of Bonn, Bonn, Germany; ;Department of Genomics, Life and Brain Center, Bonn, Germany; ;Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland; ;Genomic Imaging, Institute of Neuroscience and Medicine, Research Center Juelich, Juelich, Germany;

http://orcid.org/0000-0002-9475-086X

Julien MendlewiczLaboratoire de Psychologie Medicale, Centre Europe´en de Psychologie Medicale, Universite´ Libre de Bruxelles and Psy Pluriel, Brussels, Belgium

Michael C. O'DonovanMRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK; ;National Centre for Mental Health, Cardiff University, Cardiff, UK;

Dan RujescuDepartment of Psychiatry, Psychotherapy, and Psychosomatics, Martin Luther University of Halle-Wittenberg, Halle, Germany; ;Department of Psychiatry, Ludwig-Maximilians-University Munich, Munich, Germany; Correspondence[email protected]

http://orcid.org/0000-0002-1432-313X

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Abstract

Objectives: Schizophrenia is a severe psychiatric disease affecting about 1% of the general population. The relative contribution of genetic factors has been estimated to be up to 80%. The mode of inheritance is complex, non-Mendelian, and in most cases involving the combined action of large numbers of genes.

Methods: This review summarises recent efforts to identify genetic variants associated with schizophrenia detected, e.g., through genome-wide association studies, studies on copy-number variants or next-generation sequencing.

Results: A large, new body of evidence on genetics of schizophrenia has accumulated over recent years. Many new robustly associated genetic loci have been detected. Furthermore, there is consensus that at least a dozen microdeletions and microduplications contribute to the disease. Genetic overlap between schizophrenia, other psychiatric disorders, and neurodevelopmental syndromes raised new questions regarding the current classification of psychiatric and neurodevelopmental diseases.

Conclusions: Future studies will address especially the functional characterisation of genetic variants. This will hopefully open the doors to our understanding of the pathophysiology of schizophrenia and other related diseases. Complementary, integrated systems biology approaches to genomics, transcriptomics, proteomics and metabolomics may also play crucial roles in enabling a precision medicine approach to the treatment of individual patients.

Keywords:

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

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Genetics of schizophrenia: A consensus paper of the WFSBP Task Force on Genetics

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