Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.
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Witt SH
Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Streit F
Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Jungkunz M
Central Institute of Mental Health, Clinic of Psychosomatic and Psychotherapeutic Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Frank J
Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Awasthi S
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
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Reinbold CS
Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
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Treutlein J
Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Degenhardt F
Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Forstner AJ
Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
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Heilmann-Heimbach S
Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Dietl L
Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
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Schwarze CE
Department of Clinical Psychology and Psychotherapy, University of Heidelberg, Heidelberg, Germany.
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Schendel D
Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Strohmaier J
Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Abdellaoui A
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
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Adolfsson R
Department of Clinical Sciences, Psychiatry, Umeå University, Umeå, Sweden.
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Air TM
Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
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Akil H
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
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Alda M
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
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Alliey-Rodriguez N
Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
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Andreassen OA
Division Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
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Babadjanova G
Institute of Pulmonology, Russian State Medical University, Moscow, Russian Federation.
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Bass NJ
Division of Psychiatry, University College London, London, UK.
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Bauer M
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Dresden, Germany.
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Baune BT
Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
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Bellivier F
Inserm, U1144, AP-HP, GH Saint-Louis, Département de Psychiatrie et de Médecine Addictologique, Paris, France.
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Bergen S
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Bethell A
National Center for Mental Health, Cardiff University, Cardiff, UK.
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Biernacka JM
Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
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Blackwood DHR
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
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Boks MP
Urain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
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Boomsma DI
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
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Børglum AD
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
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Borrmann-Hassenbach M
Medical and Quality Assurance, Clinics of Upper Bavaria, Munich, Germany.
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Brennan P
Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
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Budde M
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Goettingen, Germany.
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Buttenschøn HN
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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Byrne EM
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
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Cervantes P
Department of Psychiatry, McGill University, Montreal, QC, Canada.
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Clarke TK
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
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Craddock N
Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
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Cruceanu C
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
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Curtis D
Centre for Psychiatry, Queen Mary University of London, London, UK.
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Czerski PM
Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
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Dannlowski U
Department of Psychiatry, University of Marburg, Marburg, Germany.
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Davis T
Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
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de Geus EJC
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
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Di Florio A
Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
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Djurovic S
Department of Medical Genetics, Oslo University Hospital Ullevål, Oslo, Norway.
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Domenici E
Centre for Integrative Biology, Università degli Studi di Trento, Trento, Italy.
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Edenberg HJ
Indiana University School of Medicine, Department of Biochemistry and Molecular Biology, Indianapolis, IN, USA.
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Etain B
Faculté de Médecine, Université Paris Est, Créteil, France.
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Fischer SB
Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
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Forty L
Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
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Fraser C
Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
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Frye MA
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
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Fullerton JM
School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
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Gade K
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Goettingen, Germany.
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Gershon ES
Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
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Giegling I
Department of Psychiatry, University of Halle, Halle, Germany.
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Gordon SD
Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
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Gordon-Smith K
Department of Psychological Medicine, University of Worcester, Worcester, UK.
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Grabe HJ
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
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Green EK
School of Biomedical and Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.
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Greenwood TA
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
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Grigoroiu-Serbanescu M
Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
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Guzman-Parra J
Mental Health Department, Biomedicine Institute, University Regional Hospital, Málaga, Spain.
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Hall LS
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
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Hamshere M
Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
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Hauser J
Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
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Hautzinger M
Department of Psychology, Eberhard Karls Universität Tübingen, Tubingen, Germany.
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Heilbronner U
Medical Center of the University of Munich, Campus Innenstadt, Institute of Psychiatric Phenomics and Genomics (IPPG), Munich, Germany.
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Herms S
Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
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Hitturlingappa S
Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
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Hoffmann P
Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
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Holmans P
Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
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Hottenga JJ
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
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Jamain S
Faculté de Médecine, Université Paris Est, Créteil, France.
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Jones I
National Center for Mental Health, Cardiff University, Cardiff, UK.
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Jones LA
Department of Psychological Medicine, University of Worcester, Worcester, UK.
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Juréus A
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Kahn RS
University Medical Center Utrecht, Division of Neuroscience, Department of Psychiatry, Utrecht, The Netherlands.
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Kammerer-Ciernioch J
Center of Psychiatry Weinsberg, Weinsberg, Germany.
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Kirov G
Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
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Kittel-Schneider S
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany.
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Kloiber S
Centre for Addiction and Mental Health, Toronto, ON, Canada.
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Knott SV
Department of Psychological Medicine, University of Worcester, Worcester, UK.
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Kogevinas M
Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
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Landén M
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Leber M
Clinic for Psychiatry and Psychotherapy, University Hospital Cologne, Cologne, Germany.
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Leboyer M
Inserm U955, Translational Psychiatry Laboratory, AP-HP, DHU PePSY, Department of Psychiatry, Université Paris Est, Créteil, France.
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Li QS
Janssen Research and Development, LLC, Neuroscience Therapeutic Area, Titusville, NJ, USA.
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Lissowska J
M. Sklodowska-Curie Cancer Center and Institute of Oncology, Cancer Epidemiology and Prevention, Warsaw, Poland.
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Lucae S
Max Planck Institute of Psychiatry, Munich, Germany.
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Martin NG
Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
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Mayoral-Cleries F
Mental Health Department, Biomedicine Institute, University Regional Hospital, Málaga, Spain.
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McElroy SL
Lindner Center of HOPE, Research Institute, Mason, OH, USA.
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McIntosh AM
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
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McKay JD
Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France.
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McQuillin A
Division of Psychiatry, University College London, London, UK.
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Medland SE
Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
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Middeldorp CM
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
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Milaneschi Y
VU University Medical Center and GGZ inGeest, Department of Psychiatry, Amsterdam, The Netherlands.
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Mitchell PB
School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
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Montgomery GW
Institute for Molecular Biology, University of Queensland, Brisbane, QLD, Australia.
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Morken G
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
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Mors O
Risskov, Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark.
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Mühleisen TW
Research Center Juelich, Institute of Neuroscience and Medicine (INM-1), Juelich, Germany.
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Müller-Myhsok B
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
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Myers RM
HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
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Nievergelt CM
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
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Nurnberger JI
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
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O'Donovan MC
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
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Loohuis LMO
Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, CA, USA.
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Ophoff R
University Medical Center Utrecht, Division of Brain Research, Utrecht, The Netherlands.
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Oruc L
Psychiatry Clinic, Clinical Center University of Sarajevo, Sarajevo, Bosnia-Herzegovina.
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Owen MJ
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
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Paciga SA
Pfizer Global Research and Development, Human Genetics and Computational Biomedicine, Groton, CT, USA.
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Penninx BWJH
VU University Medical Center and GGZ inGeest, Department of Psychiatry, Amsterdam, The Netherlands.
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Perry A
Department of Psychological Medicine, University of Worcester, Worcester, UK.
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Pfennig A
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Dresden, Germany.
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Potash JB
Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
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Preisig M
Department of Psychiatry, Psychiatric University Hospital of Lausanne, Lausanne, Switzerland.
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Reif A
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany.
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Rivas F
Mental Health Department, Biomedicine Institute, University Regional Hospital, Málaga, Spain.
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Rouleau GA
Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, QC, Canada.
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Schofield PR
School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
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Schulze TG
Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Schwarz M
Psychiatric Center Nordbaden, Wiesloch, Germany.
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Scott L
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
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Sinnamon GCB
School of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia.
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Stahl EA
Broad Institute of MIT and Harvard, Medical and Population Genetics, Cambridge, MA, USA.
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Strauss J
Centre for Addiction and Mental Health, Toronto, ON, Canada.
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Turecki G
Department of Psychiatry, McGill University, Montreal, QC, Canada.
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Van der Auwera S
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
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Vedder H
Psychiatric Center Nordbaden, Wiesloch, Germany.
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Vincent JB
Centre for Addiction and Mental Health, Molecular Neuropsychiatry and Development Laboratory, Toronto, ON, Canada.
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Willemsen G
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
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Witt CC
Department of Anaesthesiology and Operative Intensive Care, University Hospital Mannheim, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
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Wray NR
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
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Xi HS
Pfizer Global Research and Development, Computational Sciences Center of Emphasis, Cambridge, MA, USA.
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Tadic A
Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Dahmen N
Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Schott BH
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
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Cichon S
University Medical Center, Department of Psychiatry and Psychotherapy, Mainz, Germany.
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Nöthen MM
Department of Psychiatry, University of Halle, Halle, Germany.
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Ripke S
University Medical Center, Department of Psychiatry and Psychotherapy, Mainz, Germany.
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Mobascher A
Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
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Rujescu D
Central Institute of Mental Health, Clinic of Psychosomatic and Psychotherapeutic Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Lieb K
Central Institute of Mental Health, Institute for Psychiatric and Psychosomatic Psychotherapy (IPPP)/Psychosomatic Medicine and Psychotherapy, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Roepke S
Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Schmahl C
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Bohus M
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Rietschel M
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Published in:
- Translational psychiatry. - 2017
English
Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10-7) and PKP4 (P=8.67 × 10-7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10-3]), SCZ (rg=0.34 [P=4.37 × 10-5]) and MDD (rg=0.57 [P=1.04 × 10-3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
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https://sonar.ch/global/documents/160173
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