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oai:repisalud.isciii.es:20.500.12105/179982024-11-28T15:48:12Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Forstner, Andreas J. author Fischer, Sascha B. author Schenk, Lorena M. author Strohmaier, Jana author Maaser-Hecker, Anna author Reinbold, Céline S. author Sivalingam, Sugirthan author Hecker, Julian author Streit, Fabian author Degenhardt, Franziska author Witt, Stephanie H. author Schumacher, Johannes author Thiele, Holger author Nürnberg, Peter author Guzman-Parra, José author Orozco Diaz, Guillermo author Auburger, Georg author Albus, Margot author Borrmann-Hassenbach, Margitta author González, Maria José author Gil Flores, Susana author Cabaleiro Fabeiro, Francisco J. author del Río Noriega, Francisco author Perez Perez, Fermin author Haro González, Jesus author Rivas, Fabio author Mayoral, Fermin author Bauer, Michael author Pfennig, Andrea author Reif, Andreas author Herms, Stefan author Hoffmann, Per author Pirooznia, Mehdi author Goes, Fernando S. author Rietschel, Marcella author Nöthen, Markus M. author Cichon, Sven authoraffiliation [Forstner,AJ; Schumacher,J] Centre for Human Genetics, University of Marburg, Marburg, Germany. [Forstner,AJ; Schenk,LM; Maaser-Hecker,A; Sivalingam,S; Degenhardt,F; Schumacher,J; Herms,S; Hoffmann,P; Nöthen,MM; Cichon,S] Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany. [Forstner,AJ; Fischer,SB; Reinbold,CS; Herms,S; Hoffmann,P; Cichon,S] Department of Biomedicine, University of Basel, Basel, Switzerland. [Forstner,AJ] Department of Psychiatry (UPK), University of Basel, Basel, Switzerland. [Fischer,SB; Reinbold,CS; Herms,S; Hoffmann,P; Cichon,S] Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. [Strohmaier,J; Streit,F; Witt,SH; Rietschel,M] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. [Strohmaier,J] SRH University Heidelberg, Academy for Psychotherapy, Heidelberg, Germany. [Reinbold,CS] Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo, Oslo, Norway. [Hecker,J] Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. [Thiele,H; Nürnberg,P] Cologne Center for Genomics, University of Cologne, Cologne, Germany. [Guzman-Parra,J; González,MJ] Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain. [Orozco Diaz,G] Unidad de Gestión Clínica del Dispositivo de Cuidados Críticos y Urgencias del Distrito Sanitario Málaga - Coin- Gudalhorce, Málaga, Spain. [Auburger,G] Experimental Neurology, Department of Neurology, Goethe University Hospital, Frankfurt am Main, Germany. [Albus,M; Borrmann-Hassenbach,M]Isar Amper Klinikum München Ost, kbo, Haar, Germany. [Gil Flores,S] Department of Mental Health, University Hospital of Reina Sofia, Cordoba, Spain. [Cabaleiro Fabeiro,FJ] Department of Mental Health, Hospital of Jaén, Jaén, Spain. [del Río Noriega,F] Department of Mental Health, Hospital of Jerez de la Frontera, Jerez de la Frontera, Spain. [Perez Perez,F] Department of Mental Health, Hospital of Puerto Real, Cádiz, Spain. [Haro González,J] Department of Mental Health, Hospital Punta de Europa, Algeciras, Spain. [Rivas,F; Mayoral,F] Department of Psychiatry, Carlos Haya Regional University Hospital, Malaga, Spain. [Bauer,M; Pfennig,A] Department of Psychiatry and Psychotherapy, Medical Faculty, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. [Reif,A] Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany. [Hoffmann,P; Cichon,S] Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany. [Pirooznia,M; Goes,FS] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA 2024-02-12T19:45:19Z 2024-02-12T19:45:19Z 2020-02-04 http://hdl.handle.net/10668/3860 http://hdl.handle.net/20.500.12105/17998 32066727 10.1038/s41398-020-0732-y 2158-3188 Translational Psychiatry Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of depression and mania. Research suggests that the cumulative impact of common alleles explains 25-38% of phenotypic variance, and that rare variants may contribute to BD susceptibility. To identify rare, high-penetrance susceptibility variants for BD, whole-exome sequencing (WES) was performed in three affected individuals from each of 27 multiply affected families from Spain and Germany. WES identified 378 rare, non-synonymous, and potentially functional variants. These spanned 368 genes, and were carried by all three affected members in at least one family. Eight of the 368 genes harbored rare variants that were implicated in at least two independent families. In an extended segregation analysis involving additional family members, five of these eight genes harbored variants showing full or nearly full cosegregation with BD. These included the brain-expressed genes RGS12 and NCKAP5, which were considered the most promising BD candidates on the basis of independent evidence. Gene enrichment analysis for all 368 genes revealed significant enrichment for four pathways, including genes reported in de novo studies of autism (padj < 0.006) and schizophrenia (padj = 0.015). These results suggest a possible genetic overlap with BD for autism and schizophrenia at the rare-sequence-variant level. The present study implicates novel candidate genes for BD development, and may contribute to an improved understanding of the biological basis of this common and often devastating disease. eng Whole exome sequencing Bipolar disorder Neuropsychiatry Genetic predisposition to disease Secuenciación del exoma completo Trastorno bipolar Neuropsiquiatría Predisposición genética a la enfermedad Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families research article