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

Nature genetics

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

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.

© 2026. The Author(s).

PMID: 42477112

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