Preben Bo Mortensen

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

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DOI

  • Till F M Andlauer, Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
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  • Jose Guzman-Parra, Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
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  • Fabian Streit, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Jana Strohmaier, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Maria José González, Department of Mental Health, Hospital of Puerto Real, Cádiz, Spain.
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  • Susana Gil Flores, Department of Mental Health, University Hospital of Reina Sofia, Córdoba, Spain.
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  • Francisco J Cabaleiro Fabeiro, Department of Mental Health, Hospital of Jaén, Jaén, Spain.
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  • Francisco Del Río Noriega, Department of Mental Health, Hospital of Jerez de la Frontera, Jerez de la Frontera, Spain.
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  • Fermin Perez Perez, Department of Mental Health, Hospital of Puerto Real, Cádiz, Spain.
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  • Jesus Haro González, Department of Mental Health, Hospital Punta de Europa, Algeciras, Spain.
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  • Guillermo Orozco Diaz, Unidad de Gestión Clínica del Dispositivo de Cuidados Críticos y Urgencias del Distrito Sanitario Málaga-Coin-Guadalhorce, Málaga, Spain.
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  • Yolanda de Diego-Otero, Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
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  • Berta Moreno-Küstner, Department of Personality, Assessment and Psychological Treatment, University of Malaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
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  • Georg Auburger, Department of Neurology, Goethe University Medical School, Frankfurt am Main, Germany.
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  • Franziska Degenhardt, Institute of Human Genetics, School of Medicine & University Hospital Bonn, University of Bonn, Bonn 53127, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn 53127, Germany.
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  • Stefanie Heilmann-Heimbach, Institute of Human Genetics, School of Medicine & University Hospital Bonn, University of Bonn, Bonn 53127, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn 53127, Germany.
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  • Stefan Herms, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; Department of Biomedicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
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  • Per Hoffmann, Institute of Human Genetics, University of Bonn, Bonn, Germany6Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany7Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
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  • Josef Frank, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Jerome C Foo, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Jens Treutlein, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Stephanie H Witt, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Sven Cichon, Institute of Human Genetics, University of Bonn, Bonn, Germany6Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany7Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
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  • Manolis Kogevinas, ISGlobal Barcelona Institute for Global Health, Doctor Aiguader 88, 08003 Barcelona, Spain; Pompeu Fabra University, Carrer Ramon Trias Fargas, 25-27, 08005 Barcelona, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Av. Monforte de Lemos, 3-5, Madrid, Spain.
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  • Fabio Rivas, Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
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  • Fermín Mayoral, Department of Mental Health, University Regional Hospital of Málaga, Institute of Biomedicine of Málaga (IBIMA), Málaga, Spain.
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  • Bertram Müller-Myhsok, University of Liverpool
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  • Andreas J Forstner, Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
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  • Markus M Nöthen, Institute of Human Genetics, School of Medicine & University Hospital Bonn, University of Bonn, Bonn 53127, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn 53127, Germany.
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  • Marcella Rietschel, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Marcella.Rietschel@zi-mannheim.de.
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  • Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

OriginalsprogEngelsk
TidsskriftMolecular Psychiatry
ISSN1359-4184
DOI
StatusE-pub ahead of print - 11 nov. 2019

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