Ina Giegling1,2, Ladislav Hosak3, Rainald Mössner4, Alessandro Serretti5, Frank Bellivier6,7, Stephan Claes8,9, David A Collier10,11, Alejo Corrales12, Lynn E DeLisi13,14, Carla Gallo15, Michael Gill16, James L Kennedy17,18,19,20, Marion Leboyer21,22,23,24, Wolfgang Maier25, Miguel Marquez26, Isabelle Massat27,28,29,30, Ole Mors31,32, Pierandrea Muglia33, Markus M Nöthen34,35, Jorge Ospina-Duque36, Michael J Owen37,38, Peter Propping39, YongYong Shi40,41,42, David St Clair43, Florence Thibaut44, Sven Cichon34,35,45,46, Julien Mendlewicz47, Michael C O'Donovan37,38, Dan Rujescu1,2. 1. a Department of Psychiatry, Psychotherapy, and Psychosomatics , Martin Luther University of Halle-Wittenberg , Halle , Germany. 2. b Department of Psychiatry , Ludwig-Maximilians-University Munich , Munich , Germany. 3. c Department of Psychiatriy , Charles University, Faculty of Medicine and University Hospital in Hradec Králové, Prague , Czech Republic. 4. d Department of Psychiatry and Psychotherapy , University of Tübingen , Tübingen , Germany. 5. e Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy. 6. f Fondation Fondamental, Créteil, France AP-HP, GH Saint-Louis-Lariboisière-Fernand-Widal, Pôle Neurosciences , Paris , France. 7. g Equipe 1, Université Paris Diderot , Paris , France. 8. h GRASP-Research Group, Department of Neuroscience , University of Leuven , Leuven , Belgium. 9. i Department of Neurosciences, University Psychiatric Center KU Leuven , Leuven , Belgium. 10. j Social, Genetic and Developmental Psychiatry Centre , Institute of Psychiatry, King's College London , London , UK. 11. k Eli Lilly and Company Ltd, Erl Wood Manor , Surrey , UK. 12. l Argentinean Association of Biological Psychiatry , National University, UNT, Buenos Aires , Argentina. 13. m VA Boston Health Care System , Brockton , MA , USA. 14. n Department of Psychiatry , Harvard Medical School , Boston , MA , USA. 15. o Departamento de Ciencias Celulares y Moleculares, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía , Universidad Peruana Cayetano Heredia , Lima , Peru. 16. p Neuropsychiatric Genetics Research Group, Department of Psychiatry , Trinity College Dublin , Dublin , Ireland. 17. q Neurogenetics Section, Centre for Addiction and Mental Health , Toronto , ON , Canada. 18. r Centre for Addiction and Mental Health , Campbell Family Mental Health Research Institute , Toronto , ON , Canada. 19. s Department of Psychiatry , University of Toronto , Toronto , ON , Canada. 20. t Collaborative Program in Neuroscience, Institute of Medical Science, University of Toronto , Toronto , ON , Canada. 21. u Equipe Psychiatrie Translationnelle, Faculté de Médecine, Université Paris-Est Créteil, Inserm U955 , Créteil , France. 22. v DHU Pe-Psy, Pôle de Psychiatrie et d'Addictologie , AP-HP, Hôpitaux Universitaires Henri Mondor , Créteil , France. 23. w Pôle de Psychiatrie , Hôpital Albert Chenevier , Créteil , France. 24. x Fondation FondaMental , Créteil , France. 25. y Department of Psychiatry and Psychotherapy , University of Bonn, Bonn , Germany. 26. z Asistencia, Docencia e Investigación en Neurociencia , Buenos Aires , Argentina. 27. aa UNI - ULB Neurosciences Institute, ULB , Bruxelles , Belgium. 28. ab National Fund of Scientific Research (FNRS) , Bruxelles , Belgium. 29. ac Laboratory of Experimental Neurology , ULB , Bruxelles , Belgium. 30. ad UR2NF - Neuropsychology and Functional Neuroimaging Research Unit, Centre de Recherche Cognition et Neurosciences , Université Libre de Bruxelles (ULB) , Bruxelles , Belgium. 31. ae Psychosis Research Unit , Aarhus University Hospital , Risskov , Denmark. 32. af The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus , Denmark. 33. ag UCB Biopharma, Brussels , Belgium. 34. ah Head, Institute of Human Genetics, University of Bonn , Bonn , Germany. 35. ai Department of Genomics , Life and Brain Center , Bonn , Germany. 36. aj Grupo de Investigación en Psiquiatría, Departamento de Psiquiatría, Facultad de Medicina , Universidad de Antioquia , Medellín , Colombia. 37. ak MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine , Cardiff University , Cardiff , UK. 38. al National Centre for Mental Health, Cardiff University , Cardiff , UK. 39. am University of Bonn, Bonn , Germany. 40. an Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education , Shanghai Jiao Tong University , Shanghai , China. 41. ao Shandong Provincial Key Laboratory of Metabloic Disease, The Affiliated Hospital of Qingdao University , Qingdao , P.R. China. 42. ap Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University , Shanghai , P.R. China. 43. aq Department of Psychiatry, University of Aberdeen, Institute of Medical Sciences , Aberdeen , UK. 44. ar INSERM U 894 Centre Psychiatry and Neurosciences , University Hospital Cochin (Site Tarnier), University Sorbonne Paris Cité (Faculty of Medicine Paris Descartes) , Paris , France. 45. as Division of Medical Genetics, Department of Biomedicine , University of Basel , Basel , Switzerland. 46. at Genomic Imaging, Institute of Neuroscience and Medicine , Research Center Juelich , Juelich , Germany. 47. au Laboratoire de Psychologie Medicale, Centre Europe´en de Psychologie Medicale , Universite´ Libre de Bruxelles and Psy Pluriel , Brussels , Belgium.
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.
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.
Authors: Teodor T Postolache; Laura Del Bosque-Plata; Serge Jabbour; Michael Vergare; Rongling Wu; Claudia Gragnoli Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2019-02-06 Impact factor: 3.568
Authors: Ivan V Pozhidaev; Anastasiia S Boiko; Anton J M Loonen; Diana Z Paderina; Olga Yu Fedorenko; Gennadiy Tenin; Elena G Kornetova; Arkadiy V Semke; Nikolay A Bokhan; Bob Wilffert; Svetlana A Ivanova Journal: Appl Clin Genet Date: 2020-04-22
Authors: Ina Giegling; Annette M Hartmann; Just Genius; Bettina Konte; Stephan Maul; Andreas Straube; Thomas Eggert; Christoph Mulert; Gregor Leicht; Susanne Karch; Ulrich Hegerl; Oliver Pogarell; Sabine M Hölter; Hans-Jürgen Möller; Jochen Graw; Dan Rujescu Journal: Transl Psychiatry Date: 2020-04-21 Impact factor: 6.222