Christoffer Tobias Witt

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • S H Witt, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • ,
  • F Streit, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • ,
  • M Jungkunz, Central Institute of Mental Health, Institute for Psychiatric and Psychosomatic Psychotherapy (IPPP)/Psychosomatic Medicine and Psychotherapy, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • ,
  • J Frank, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • ,
  • S Awasthi, Charité – Universitätsmedizin Berlin
  • ,
  • C S Reinbold, Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • ,
  • J Treutlein, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • ,
  • F Degenhardt, Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
  • ,
  • A J Forstner, Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
  • ,
  • S Heilmann-Heimbach, s Institute of Human Genetics , University of Bonn , Bonn , Germany.
  • ,
  • L Dietl, Charité – Universitätsmedizin Berlin
  • ,
  • C E Schwarze, Department of Clinical Psychology and Psychotherapy, University of Heidelberg, Heidelberg, Germany.
  • ,
  • D Schendel
  • J Strohmaier, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, Germany.
  • ,
  • A Abdellaoui, Vrije Universiteit Amsterdam
  • ,
  • R Adolfsson, Department of Clinical Sciences, Psychiatry, Umeå University, Umeå, Sweden.
  • ,
  • T M Air, University of Adelaide
  • ,
  • H Akil, University of Michigan, Ann Arbor
  • ,
  • M Alda, Dalhousie University
  • ,
  • N Alliey-Rodriguez, Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
  • ,
  • O A Andreassen, K. G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway ; Department of Psychology, University of Oslo, Oslo, Norway.
  • ,
  • G Babadjanova, Institute of Pulmonology, Russian State Medical University, Moscow, Russian Federation.
  • ,
  • N J Bass, Molecular Psychiatry Laboratory, Division of Psychiatry, University College London
  • ,
  • M Bauer, Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
  • ,
  • B T Baune, University of Adelaide
  • ,
  • F Bellivier, Inserm, U1144, AP-HP, GH Saint-Louis, Département de Psychiatrie et de Médecine Addictologique, Paris, France.
  • ,
  • S Bergen, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • ,
  • A Bethell, Cardiff University
  • ,
  • J M Biernacka, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
  • ,
  • D H R Blackwood, Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
  • ,
  • M P Boks, Urain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
  • ,
  • D I Boomsma, Vrije Universiteit Amsterdam
  • ,
  • A D Børglum
  • M Borrmann-Hassenbach, Medical and Quality Assurance, Clinics of Upper Bavaria, Munich, Germany.
  • ,
  • P Brennan, Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France.
  • ,
  • M Budde, Department of Psychiatry and Psychotherapy, University Medical Center Georg-August-Universität, Göttingen, Germany., Medical Center of the University of Munich, Campus Innenstadt, Institute of Psychiatric Phenomics and Genomics (IPPG), Munich, Germany.
  • ,
  • H N Buttenschøn
  • E M Byrne, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
  • ,
  • P Cervantes, Department of Psychiatry, McGill University, Montreal, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
  • ,
  • T-K Clarke, Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
  • ,
  • S B Fischer, Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • ,
  • K Gade, Department of Psychiatry and Psychotherapy, University Medical Center Georg-August-Universität, Göttingen, Germany., Medical Center of the University of Munich, Campus Innenstadt, Institute of Psychiatric Phenomics and Genomics (IPPG), Munich, Germany.
  • ,
  • L S Hall, Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom., Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne
  • ,
  • P Hoffmann, Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland., s Institute of Human Genetics , University of Bonn , Bonn , Germany., Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
  • ,
  • L A Jones, Department of Psychological Medicine, University of Worcester, Worcester, UK.
  • ,
  • Q S Li, Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA.
  • ,
  • O Mors
  • M Schwarz, Psychiatric Center Nordbaden, Wiesloch, Germany.
  • ,
  • E A Stahl, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • ,
  • C C Witt
  • Bipolar Disorders Working Group of the Psychiatric Genomics Consortium

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.

Original languageEnglish
JournalTranslational Psychiatry
Volume7
Issue6
Pages (from-to)e1155
ISSN2158-3188
DOIs
Publication statusPublished - 20 Jun 2017

    Research areas

  • Journal Article

See relations at Aarhus University Citationformats

ID: 120344445