Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families
| Autor: | Fermín Mayoral, Fabio Rivas, Jesus Haro González, Franziska Degenhardt, Julian Hecker, Fermin Perez Perez, Marcella Rietschel, Michael Bauer, Margot Albus, Markus M. Nöthen, Sascha B. Fischer, Susana Gil Flores, Francisco del Río Noriega, Mehdi Pirooznia, Stefan Herms, Jana Strohmaier, Stephanie H. Witt, Fernando S. Goes, Margitta Borrmann-Hassenbach, Anna Maaser-Hecker, Sugirthan Sivalingam, Sven Cichon, Lorena M. Schenk, Georg Auburger, Andreas Reif, Fabian Streit, María González, Francisco J. Cabaleiro Fabeiro, Peter Nürnberg, Jose Guzman-Parra, Andreas J. Forstner, Holger Thiele, Guillermo Orozco Diaz, Andrea Pfennig, Céline S. Reinbold, Johannes Schumacher, Per Hoffmann |
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| Přispěvatelé: | [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, Cichon,S] Department of Biomedicine, University of Basel, Basel, Switzerland. [Forstner,AJ] Department of Psychiatry (UPK), University of Basel, Basel, Switzerland. [Fischer,SB, 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, The study was supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A/01ZX1614A to M.M.N. Forstner et al. Translational Psychiatry (2020) 10:57 Page 8 of 10 and S.C., grant 01ZX1314G/01ZX1614G to M.R.) and through ERA-NET NEURON, 'SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation' (01EW1810 to MR). The study was also supported by the German Research Foundation (DFG, grant FOR2107, RI908/11-1 and RI908/11–2 to M.R., NO246/10-1 and NO 246/10-2 to M.M.N.), and the Swiss National Science Foundation (SNSF, grant 156791 to S.C.). M.M.N. is a member of the DFG-funded Excellence-Cluster ImmunoSensation. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Candidate gene
Bipolar Disorder Psychiatry and Psychology::Mental Disorders::Mood Disorders::Affective Disorders Psychotic::Bipolar Disorder [Medical Subject Headings] Neuropsiquiatría Disease Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] 0302 clinical medicine Germany Exome Exome sequencing Genetics 0303 health sciences Trastorno bipolar Predisposición genética a la enfermedad Neuropsychiatry Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings] 3. Good health Pedigree Psychiatry and Mental health Schizophrenia Phenomena and Processes::Genetic Phenomena::Inheritance Patterns::Penetrance [Medical Subject Headings] Psychiatry and Psychology::Mental Disorders::Mental Disorders Diagnosed in Childhood::Child Development Disorders Pervasive::Autistic Disorder [Medical Subject Headings] Biology Molecular neuroscience Article Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Exome [Medical Subject Headings] lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience Exome Sequencing medicine Psychiatry and Psychology::Mental Disorders::Schizophrenia and Disorders with Psychotic Features::Schizophrenia [Medical Subject Headings] Humans Genetic Predisposition to Disease Bipolar disorder ddc:610 Allele Gene lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry 030304 developmental biology Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings] Secuenciación del exoma completo Whole exome sequencing Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings] medicine.disease Geographical Locations::Geographic Locations::Europe::Germany [Medical Subject Headings] Autism 030217 neurology & neurosurgery RGS Proteins |
| Zdroj: | Translational Psychiatry, Vol 10, Iss 1, Pp 1-10 (2020) Translational Psychiatry 10, 59 (2020). doi:10.1038/s41398-020-0732-y Translational Psychiatry 10(1), 57 (2020). doi:10.1038/s41398-020-0732-y Translational Psychiatry |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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