| Title: | Genome-wide association analyses of borderline personality disorder identify 11 loci and highlight shared risk with mental and somatic disorders |
| Journal: | Nature Genetics |
| Published: | 20 Jul 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42477112/ |
| DOI: | https://doi.org/10.1038/s41588-026-02654-3 |
| URL: | https://www.nature.com/articles/s41588-026-02654-3.pdf |
Publication 21430
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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.</p>
15 Keywords
- Attention Deficit Disorder with Hyperactivity
- Borderline Personality Disorder
- Case-Control Studies
- Female
- Genetic Loci
- Genetic Predisposition to Disease
- Genetic Risk Score
- Genome-Wide Association Study
- Humans
- Male
- Multifactorial Inheritance
- Phenotype
- Polymorphism, Single Nucleotide
- Risk Factors
- Stress Disorders, Post-Traumatic
151 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
- Henrik Hjalgrim
- Christopher Hübel
- Gitta A. Jacob
- Bitten Aagaard
- Anders Jorgensen
- Martin Jungkunz
- Nikolaus Kleindienst
- Nora Knoblich
- Stefanie Koglin
- Julia Kraft
- Kristi Krebs
- Christopher W. Lee
- Yuhao Lin
- Stefanie Lis
- Amanda Lisoway
- Ioannis A. Malogiannis
- Amy Martinsen
- Tolou Maslahati
- Katharina Merz
- Andreas Meyer-Lindenberg
- Susan Mikkelsen
- Christina Mikkelsen
- Arian Mobascher
- Gerard Muntané
- Asmundur Oddsson
- Sisse R. Ostrowski
- Teemu Palviainen
- Ole B. V. Pedersen
- Geir Pedersen
- Liam Quinn
- Matthias A. Reinhard
- Florian A. Ruths
- Björn H. Schott
- Michael Schredl
- Emanuel Schwarz
- Cornelia E. Schwarze
- Michael Schwinn
- Tabea Sarah Send
- Engilbert Sigurdsson
- Katja Simon-Keller
- Astros T. Skuladottir
- Joaquim Soler
- Anne Sonley
- Erik Sørensen
- Hreinn Stefansson
- Peter Straub
- Jaana Suvisaari
- Martin Tesli
- Jacob Træholt
- Henrik Ullum
- Maja P. Völker
- G. Bragi Walters
- Rujia Wang
- Christian C. Witt
- Gerhard Zarbock
- Peter Zill
- John-Anker Zwart
- Ole A. Andreassen
- Arnoud Arntz
- Joanna M. Biernacka
- Martin Bohus
- Gerome Breen
- Alexander L. Chapman
- Sven Cichon
- Lea K. Davis
- Michael Deuschle
- Sebastian Euler
- Sabine C. Herpertz
- Benjamin Hummelen
- Andrea Jobst
- Jaakko Kaprio
- James L. Kennedy
- Kelli Lehto
- Klaus Lieb
- Lourdes Martorell
- Shelley McMain
- Richard Musil
- Vanessa Nieratschker
- Markus M. Nöthen
- Frank Padberg
- Aarno Palotie
- Juan C. Pascual
- Nader Perroud
- Josep A. Ramos-Quiroga
- Ted Reichborn-Kjennerud
- Marta Ribases
- Stefan Roepke
- Dan Rujescu
- Sandra Sanchez-Roige
- Claudia Schilling
- Christian Schmahl
- Kari Stefansson
- Thorgeir E. Thorgeirsson
- Gustavo Turecki
- Elisabet Vilella
- Thomas Werge
- Bendik S. Winsvold
- Johannes Wrege
- Marcella Rietschel
- Stephan Ripke
- Stephanie H. Witt
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