Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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28632202
TITLE
Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.
ABSTRACT
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.
DATE PUBLISHED
2017 Jun 20
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/02/16
accepted 2017/04/10
entrez 2017/06/21 06:00
pubmed 2017/06/21 06:00
medline 2017/06/21 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Witt SH Witt S H SH Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Streit F Streit F F Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Jungkunz M Jungkunz M M Central Institute of Mental Health, Institute for Psychiatric and Psychosomatic Psychotherapy (IPPP)/Psychosomatic Medicine and Psychotherapy, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Frank J Frank J J Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Awasthi S Awasthi S S Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Reinbold CS Reinbold C S CS Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
Treutlein J Treutlein J J Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Degenhardt F Degenhardt F F Life and Brain Center, Department of Genomics, University of Bonn, Bonn, Germany.
Forstner AJ Forstner A J AJ Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
Heilmann-Heimbach S Heilmann-Heimbach S S Institute of Human Genetics, University of Bonn, Bonn, Germany.
Dietl L Dietl L L Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Schwarze CE Schwarze C E CE Department of Clinical Psychology and Psychotherapy, University of Heidelberg, Heidelberg, Germany.
Schendel D Schendel D D Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Strohmaier J Strohmaier J J Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Abdellaoui A Abdellaoui A A Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Adolfsson R Adolfsson R R Department of Clinical Sciences, Psychiatry, Umeå University, Umeå, Sweden.
Air TM Air T M TM Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Akil H Akil H H Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Alda M Alda M M Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Alliey-Rodriguez N Alliey-Rodriguez N N Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
Andreassen OA Andreassen O A OA NORMENT, University of Oslo, Oslo, Norway.
Babadjanova G Babadjanova G G Institute of Pulmonology, Russian State Medical University, Moscow, Russian Federation.
Bass NJ Bass N J NJ Division of Psychiatry, University College London, London, UK.
Bauer M Bauer M M Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Dresden, Germany.
Baune BT Baune B T BT Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Bellivier F Bellivier F F Inserm, U1144, AP-HP, GH Saint-Louis, Département de Psychiatrie et de Médecine Addictologique, Paris, France.
Bergen S Bergen S S Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Bethell A Bethell A A National Center for Mental Health, Cardiff University, Cardiff, UK.
Biernacka JM Biernacka J M JM Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Blackwood DHR Blackwood D H R DHR Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Boks MP Boks M P MP Urain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
Boomsma DI Boomsma D I DI Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Børglum AD Børglum A D AD iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
Borrmann-Hassenbach M Borrmann-Hassenbach M M Medical and Quality Assurance, Clinics of Upper Bavaria, Munich, Germany.
Brennan P Brennan P P Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
Budde M Budde M M Medical Center of the University of Munich, Campus Innenstadt, Institute of Psychiatric Phenomics and Genomics (IPPG), Munich, Germany.
Buttenschøn HN Buttenschøn H N HN Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Byrne EM Byrne E M EM Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Cervantes P Cervantes P P Department of Psychiatry, McGill University, Montreal, QC, Canada.
Clarke TK Clarke T-K TK Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Craddock N Craddock N N Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Cruceanu C Cruceanu C C Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Curtis D Curtis D D UCL Genetics Institute, University College London, London, UK.
Czerski PM Czerski P M PM Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Dannlowski U Dannlowski U U Department of Psychiatry, University of Münste, Münster, Germany.
Davis T Davis T T Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
de Geus EJC de Geus E J C EJC Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Di Florio A Di Florio A A Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Djurovic S Djurovic S S NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
Domenici E Domenici E E Centre for Integrative Biology, Università degli Studi di Trento, Trento, Italy.
Edenberg HJ Edenberg H J HJ Indiana University School of Medicine, Department of Medical and Molecular Genetics, Indianapolis, IN, USA.
Etain B Etain B B Faculté de Médecine, Université Paris Est, Créteil, France.
Fischer SB Fischer S B SB Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
Forty L Forty L L Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Fraser C Fraser C C Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Frye MA Frye M A MA Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
Fullerton JM Fullerton J M JM Neuroscience Research Australia, Sydney, NSW, Australia.
Gade K Gade K K Medical Center of the University of Munich, Campus Innenstadt, Institute of Psychiatric Phenomics and Genomics (IPPG), Munich, Germany.
Gershon ES Gershon E S ES Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
Giegling I Giegling I I Department of Psychiatry, University of Halle, Halle, Germany.
Gordon SD Gordon S D SD Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Gordon-Smith K Gordon-Smith K K Department of Psychological Medicine, University of Worcester, Worcester, UK.
Grabe HJ Grabe H J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Green EK Green E K EK School of Biomedical and Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.
Greenwood TA Greenwood T A TA Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Grigoroiu-Serbanescu M Grigoroiu-Serbanescu M M Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
Guzman-Parra J Guzman-Parra J J Mental Health Department, Biomedicine Institute, University Regional Hospital, Málaga, Spain.
Hall LS Hall L S LS Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Hamshere M Hamshere M M Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Hauser J Hauser J J Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Hautzinger M Hautzinger M M Department of Psychology, Eberhard Karls Universität Tübingen, Tubingen, Germany.
Heilbronner U Heilbronner U U Medical Center of the University of Munich, Campus Innenstadt, Institute of Psychiatric Phenomics and Genomics (IPPG), Munich, Germany.
Herms S Herms S S Life and Brain Center, Department of Genomics, University of Bonn, Bonn, Germany.
Hitturlingappa S Hitturlingappa S S Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Hoffmann P Hoffmann P P Life and Brain Center, Department of Genomics, University of Bonn, Bonn, Germany.
Holmans P Holmans P P Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Hottenga JJ Hottenga J-J JJ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Jamain S Jamain S S Inserm U955, Psychiatrie Translationnelle, Créteil, France.
Jones I Jones I I National Center for Mental Health, Cardiff University, Cardiff, UK.
Jones LA Jones L A LA Department of Psychological Medicine, University of Worcester, Worcester, UK.
Juréus A Juréus A A Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Kahn RS Kahn R S RS University Medical Center Utrecht, Division of Neuroscience, Department of Psychiatry, Utrecht, The Netherlands.
Kammerer-Ciernioch J Kammerer-Ciernioch J J Center of Psychiatry Weinsberg, Weinsberg, Germany.
Kirov G Kirov G G Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Kittel-Schneider S Kittel-Schneider S S Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany.
Kloiber S Kloiber S S Max Planck Institute of Psychiatry, Munich, Germany.
Knott SV Knott S V SV Department of Psychological Medicine, University of Worcester, Worcester, UK.
Kogevinas M Kogevinas M M Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Landén M Landén M M Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Leber M Leber M M Clinic for Psychiatry and Psychotherapy, University Hospital Cologne, Cologne, Germany.
Leboyer M Leboyer M M Inserm U955, Translational Psychiatry Laboratory, AP-HP, DHU PePSY, Department of Psychiatry, Université Paris Est, Créteil, France.
Li QS Li Q S QS Janssen Research and Development, LLC, Neuroscience Therapeutic Area, Titusville, NJ, USA.
Lissowska J Lissowska J J M. Sklodowska-Curie Cancer Center and Institute of Oncology, Cancer Epidemiology and Prevention, Warsaw, Poland.
Lucae S Lucae S S Max Planck Institute of Psychiatry, Munich, Germany.
Martin NG Martin N G NG School of Psychology, The University of Queensland, Brisbane, QLD, Australia.
Mayoral-Cleries F Mayoral-Cleries F F Mental Health Department, Biomedicine Institute, University Regional Hospital, Málaga, Spain.
McElroy SL McElroy S L SL Lindner Center of HOPE, Research Institute, Mason, OH, USA.
McIntosh AM McIntosh A M AM Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
McKay JD McKay J D JD Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France.
McQuillin A McQuillin A A Division of Psychiatry, University College London, London, UK.
Medland SE Medland S E SE Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Middeldorp CM Middeldorp C M CM Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Milaneschi Y Milaneschi Y Y VU University Medical Center and GGZ inGeest, Department of Psychiatry, Amsterdam, The Netherlands.
Mitchell PB Mitchell P B PB Black Dog Institute, Sydney, NSW, Australia.
Montgomery GW Montgomery G W GW Institute for Molecular Biology, University of Queensland, Brisbane, QLD, Australia.
Morken G Morken G G Department of Psychiatry, St Olavs University Hospital, Trondheim, Norway.
Mors O Mors O O iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Mühleisen TW Mühleisen T W TW Division of Medical Genetics, University of Basel, Basel, Switzerland.
Müller-Myhsok B Müller-Myhsok B B University of Liverpool, Liverpool, UK.
Myers RM Myers R M RM HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
Nievergelt CM Nievergelt C M CM Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Nurnberger JI Nurnberger J I JI Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
O'Donovan MC O'Donovan M C MC MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Loohuis LMO Loohuis L M O LMO Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, CA, USA.
Ophoff R Ophoff R R University Medical Center Utrecht, Division of Brain Research, Utrecht, The Netherlands.
Oruc L Oruc L L Psychiatry Clinic, Clinical Center University of Sarajevo, Sarajevo, Bosnia-Herzegovina.
Owen MJ Owen M J MJ MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Paciga SA Paciga S A SA Pfizer Global Research and Development, Human Genetics and Computational Biomedicine, Groton, CT, USA.
Penninx BWJH Penninx B W J H BWJH VU University Medical Center and GGZ inGeest, Department of Psychiatry, Amsterdam, The Netherlands.
Perry A Perry A A Department of Psychological Medicine, University of Worcester, Worcester, UK.
Pfennig A Pfennig A A Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Dresden, Germany.
Potash JB Potash J B JB Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
Preisig M Preisig M M Department of Psychiatry, Psychiatric University Hospital of Lausanne, Lausanne, Switzerland.
Reif A Reif A A Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt am Main, Germany.
Rivas F Rivas F F Mental Health Department, Biomedicine Institute, University Regional Hospital, Málaga, Spain.
Rouleau GA Rouleau G A GA Montreal Neurological Institute and Hospital, Montreal, QC, Canada.
Schofield PR Schofield P R PR Neuroscience Research Australia, Sydney, NSW, Australia.
Schulze TG Schulze T G TG NIMH Division of Intramural Research Programs, Human Genetics Branch, Bethesda, MD, USA.
Schwarz M Schwarz M M Psychiatric Center Nordbaden, Wiesloch, Germany.
Scott L Scott L L Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Sinnamon GCB Sinnamon G C B GCB School of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia.
Stahl EA Stahl E A EA Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Strauss J Strauss J J Centre for Addiction and Mental Health, Toronto, ON, Canada.
Turecki G Turecki G G Department of Psychiatry, McGill University, Montreal, QC, Canada.
Van der Auwera S Van der Auwera S S Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Vedder H Vedder H H Psychiatric Center Nordbaden, Wiesloch, Germany.
Vincent JB Vincent J B JB Centre for Addiction and Mental Health, Molecular Neuropsychiatry and Development Laboratory, Toronto, ON, Canada.
Willemsen G Willemsen G G Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Witt CC Witt C C CC Department of Anaesthesiology and Operative Intensive Care, University Hospital Mannheim, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Wray NR Wray N R NR Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Xi HS Xi H S HS Pfizer Global Research and Development, Computational Sciences Center of Emphasis, Cambridge, MA, USA.
Bipolar Disorders Working Group of the Psychiatric Genomics Consortium
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Tadic A Tadic A A University Medical Center, Department of Psychiatry and Psychotherapy, Mainz, Germany.
Dahmen N Dahmen N N University Medical Center, Department of Psychiatry and Psychotherapy, Mainz, Germany.
Schott BH Schott B H BH Leibniz Institute for Neurobiology, Magdeburg, Germany.
Cichon S Cichon S S Department of Biomedicine, University of Basel, Basel, Switzerland.
Nöthen MM Nöthen M M MM Life and Brain Center, Department of Genomics, University of Bonn, Bonn, Germany.
Ripke S Ripke S S Analytic and Translational Genetics Unit, Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
Mobascher A Mobascher A A University Medical Center, Department of Psychiatry and Psychotherapy, Mainz, Germany.
Rujescu D Rujescu D D Department of Psychiatry, University of Halle, Halle, Germany.
Lieb K Lieb K K University Medical Center, Department of Psychiatry and Psychotherapy, Mainz, Germany.
Roepke S Roepke S S Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Schmahl C Schmahl C C Central Institute of Mental Health, Clinic of Psychosomatic and Psychotherapeutic Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Bohus M Bohus M M Central Institute of Mental Health, Institute for Psychiatric and Psychosomatic Psychotherapy (IPPP)/Psychosomatic Medicine and Psychotherapy, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Rietschel M Rietschel M M Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
INVESTIGATORS
JOURNAL
VOLUME: 7
ISSUE: 6
TITLE: Translational psychiatry
ISOABBREVIATION: Transl Psychiatry
YEAR: 2017
MONTH: Jun
DAY: 20
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2158-3188
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Transl Psychiatry
COUNTRY: United States
ISSNLINKING: 2158-3188
NLMUNIQUEID: 101562664
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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