Journal Article

DZNE-2026-00873

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genome-wide association analyses of borderline personality disorder identify 11 loci and highlight shared risk with mental and somatic disorders.

Streit, F. ; Awasthi, S. ; Hall, A. S. M. ; Braun, A. ; Niarchou, M. ; Marouli, E. ; Babajide, O. ; Frank, J. ; Zillich, L. ; Callies, C. M. ; Avetyan, D. ; Zillich, E. ; Naamanka, J. ; Gonzalez, J. ; Harder, A. ; Lu, Y. ; Aherrahrou, Z. ; Ahmad, Z.-U.-A. ; Ask, H. ; Batzler, A. ; Benros, M. E. ; Brand-de Wilde, O. M. ; Brunak, S. ; Bruun, M. T. ; Christoffersen, L. A. N. ; Colodro-Conde, L. ; Coombes, B. J. ; Corfield, E. C. ; Dahmen, N. ; Didriksen, M. ; Dinh, K. M. ; Djurovic, S. ; Dowsett, J. ; Drange, O. K. ; Dukal, H. ; Edelmann, S. ; Erikstrup, C. ; Espinola, M. K. ; Fassbinder, E. ; Faucon, A. ; Ferreira de Sá, D. S. ; Foo, J. C. ; Gilles, M. ; Gutiérrez-Zotes, A. ; Hansen, T. F. ; Haraldsson, M. ; Harper, R. P. ; Havdahl, A. ; Heilbronner, U. ; Herms, S. ; Hjalgrim, H. ; Hübel, C. ; Jacob, G. A. ; Aagaard, B. ; Jorgensen, A. ; Jungkunz, M. ; Kleindienst, N. ; Knoblich, N. ; Koglin, S. ; Kraft, J. ; Krebs, K. ; Lee, C. W. ; Lin, Y. ; Lis, S. ; Lisoway, A. ; Malogiannis, I. A. ; Martinsen, A. ; Maslahati, T. ; Merz, K. ; Meyer-Lindenberg, A. ; Mikkelsen, S. ; Mikkelsen, C. ; Mobascher, A. ; Muntané, G. ; Oddsson, A. ; Ostrowski, S. R. ; Palviainen, T. ; Pedersen, O. B. V. ; Pedersen, G. ; Quinn, L. ; Reinhard, M. A. ; Ruths, F. A. ; Schott, B. H.DZNE* ; Schredl, M. ; Schwarz, E. ; Schwarze, C. E. ; Schwinn, M. ; Send, T. S. ; Sigurdsson, E. ; Simon-Keller, K. ; Skuladottir, A. T. ; Soler, J. ; Sonley, A. ; Sørensen, E. ; Stefansson, H. ; Straub, P. ; Suvisaari, J. ; Tesli, M. ; Træholt, J. ; Ullum, H. ; Völker, M. P. ; Walters, G. B. ; Wang, R. ; Witt, C. C. ; Zarbock, G. ; Zill, P. ; Zwart, J.-A. ; Consortium, D. G. (Collaboration Author) ; Study, G. (Collaboration Author) ; Psychiatry, H. A. (Collaboration Author) ; Andreassen, O. A. ; Arntz, A. ; Biernacka, J. M. ; Bohus, M. ; Breen, G. ; Chapman, A. L. ; Cichon, S. ; Davis, L. K. ; Deuschle, M. ; Euler, S. ; Herpertz, S. C. ; Hummelen, B. ; Jobst, A. ; Kaprio, J. ; Kennedy, J. L. ; Lehto, K. ; Lieb, K. ; Martorell, L. ; McMain, S. ; Musil, R. ; Nieratschker, V. ; Nöthen, M. M. ; Padberg, F. ; Palotie, A. ; Pascual, J. C. ; Perroud, N. ; Ramos-Quiroga, J. A. ; Reichborn-Kjennerud, T. ; Ribases, M. ; Roepke, S. ; Rujescu, D. ; Sanchez-Roige, S. ; Schilling, C. ; Schmahl, C. ; Stefansson, K. ; Thorgeirsson, T. E. ; Turecki, G. ; Vilella, E. ; Werge, T. ; Winsvold, B. S. ; Wrege, J. ; Rietschel, M. ; Ripke, S. ; Witt, S. H.

2026
Macmillan Publishers Limited, part of Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41588-026-02654-3

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.

Keyword(s): Humans (MeSH) ; Genome-Wide Association Study (MeSH) ; Borderline Personality Disorder: genetics (MeSH) ; Genetic Predisposition to Disease: genetics (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Genetic Risk Score (MeSH) ; Multifactorial Inheritance: genetics (MeSH) ; Risk Factors (MeSH) ; Stress Disorders, Post-Traumatic: genetics (MeSH) ; Female (MeSH) ; Male (MeSH) ; Genetic Loci (MeSH) ; Case-Control Studies (MeSH) ; Attention Deficit Disorder with Hyperactivity: genetics (MeSH) ; Phenotype (MeSH)

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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