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Journal Article Ahead of print 1 citation

PubMed: 42477112 DOI: 10.1038/s41588-026-02654-3

Genome-wide association analyses of borderline personality disorder identify 11 loci and highlight shared risk with mental and somatic disorders.

Nat Genet

Authors: Fabian Streit, Swapnil Awasthi, Alisha S M Hall, Alice Braun, Maria Niarchou, Eirini Marouli, Oladapo Babajide, Josef Frank, Lea Zillich, Carolin M Callies, Diana Avetyan, Eric Zillich, Joonas Naamanka, Jean Gonzalez, Arvid Harder, Yi Lu, Zouhair Aherrahrou, Zain-Ul-Abideen Ahmad, Helga Ask, Anthony Batzler, Michael E Benros, Odette M Brand-de Wilde, Søren Brunak, Mie T Bruun, Lea A N Christoffersen, Lucía Colodro-Conde, Brandon J Coombes, Elizabeth C Corfield, Norbert Dahmen, Maria Didriksen, Khoa M Dinh, Srdjan Djurovic, Joseph Dowsett, Ole Kristian Drange, Helene Dukal, Susanne Edelmann, Christian Erikstrup, Mariana K Espinola, Eva Fassbinder, Annika Faucon, Diana S Ferreira de Sá, Jerome C Foo, Maria Gilles, Alfonso Gutiérrez-Zotes, Thomas F Hansen, Magnus Haraldsson, R Patrick Harper, Alexandra Havdahl, Urs Heilbronner, Stefan Herms … and 101 other authors

Affiliations

  • Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • German Center for Mental Health (DZPG), Partner Site Mannheim-Heidelberg-Ulm, Mannheim-Heidelberg-Ulm, Germany.
  • Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
  • Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Department of Affective Disorders, Aarhus University Hospital-Psychiatry, Aarhus, Denmark.
  • Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University London, London, UK.
  • Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • German Center for Mental Health (DZPG), Partner Site Mannheim-Heidelberg-Ulm, Mannheim-Heidelberg-Ulm, Germany.
  • Hector Institute for Translational Brain Research, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Health Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany.
  • Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
  • Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
  • DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany.
  • University Heart Center Lübeck, Lübeck, Germany.
  • Social, Genetic and Developmental Psychiatry Centre, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK.
  • PsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
  • Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway.
  • PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
  • Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
  • Copenhagen Research Centre for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
  • Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Netherlands Institute for Personality Disorders, Halsteren, Netherlands.
  • Department of Public Health & Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Clinical Immunology Research Unit, Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
  • Department of Clinical Immunology, Zealand University Hospital, Køge, Denmark.
  • Institute of Biological Psychiatry, Mental Health Services, University of Copenhagen, Copenhagen, Denmark.
  • Brain and Mental Health Research Program, QIMR Berghofer, Brisbane, Queensland, Australia.
  • School of Psychology, The University of Queensland, Brisbane, Queensland, Australia.
  • Psychiatric Genetic Epidemiology Group, Research Department & Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo, Norway.
  • MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Department of Psychiatry and Psychotherapy, University Medical Center, University of Mainz, Mainz, Germany.
  • Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
  • Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
  • Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Department of Psychiatry, Sørlandet Hospital, Kristiansand, Agder, Norway.
  • Department of Psychiatry and Psychotherapy, University Hospital Tübingen, Tübingen, Germany.
  • German Center for Mental Health (DZPG), partner site Tübingen, Tübingen, Germany.
  • Department of Psychiatry and Psychotherapy, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.
  • Department of Psychology, Division of Clinical Psychology and Psychotherapy, Saarland University, Saarbrücken, Germany.
  • Institute for Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Department of Psychiatry, College of Health Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Hospital Universitari Institut Pere Mata (HUIPM), Institute de Recerca Biomédica Catalunya Sud (IRB-CatSud) previously IISPV-CERCA, Universitat Rovira i Virgili (URV), Reus, Spain.
  • Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
  • Neurogenomic, Translational Research Centre, Copenhagen University Hospital, Glostrup, Denmark.
  • Danish Headache Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Landspitali University Hospital, Reykjavik, Iceland.
  • Faculty of Medicine, Department of Psychiatry, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
  • Bradford District Care NHS Foundation Trust, Bradford, UK.
  • Institute of Psychiatric Phenomics and Genomics (IPPG), LMU University Hospital, LMU Munich, Munich, Germany.
  • Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Institute of Human Genetics, University Hospital Bonn & University of Bonn, Bonn, Germany.

Abstract

Borderline personality disorder (BPD) is a severe mental health condition influenced by environmental risk factors (for example, interpersonal trauma) and genetic factors. We conducted the largest genome-wide association study (GWAS) meta-analysis of BPD so far, with a discovery sample of 12,339 cases and 1,041,717 controls, and a replication study of 685 cases and 107,750 controls (all participants of European ancestry). We identified 11 independent associated genomic loci and 9 risk genes in gene-based analyses. We observed a single-nucleotide polymorphism heritability of 17.3% and derived polygenic scores (PGS) that predicted 4.6% of the phenotypic variance in BPD on the liability scale. BPD showed the strongest positive genetic correlations with GWAS of post-traumatic stress disorder, depression, attention deficit hyperactivity disorder, antisocial behavior, and measures of suicide and self-harm. Phenome-wide analyses in Vanderbilt University Medical Center Biobank and UK Biobank using BPD-PGS confirmed these associations and also identified associations with other medical conditions, including obstructive pulmonary disease and diabetes. These analyses highlight BPD as a polygenic disorder, with the genetic risk showing substantial overlap with psychiatric and physical health conditions.

MeSH

Genes, Personality Disorders, Borderline Personality Disorder, Personality, Genome, Stress Disorders, Traumatic, Wounds And Injuries