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Genome-wide association study of borderline personality disorder identifies 11 loci and highlights shared risk with mental and somatic disorders.

medRxiv : the preprint server for health sciences

Authors: Fabian Streit, Swapnil Awasthi, Alisha Sm 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 An 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 Bv Pedersen, Geir Pedersen, Liam Quinn, Matthias A Reinhard, Florian A Ruths, Björn H Schott, Michael Schredl, Emanuel Schwarz, Cornelia E Schwarze, Michael Schwinn, Tabea 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

We conducted the largest genome-wide meta-analysis of borderline personality disorder (BPD) to date, 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 nine risk genes in the gene-based analysis. We observed a single-nucleotide polymorphism (SNP) heritability of 17.3% and derived polygenic scores (PGS) predicted 4.6% of the phenotypic variance in BPD on the liability scale. BPD showed the strongest positive genetic correlations with GWAS of posttraumatic stress disorder, depression, attention deficit hyperactivity disorder, antisocial behavior, and measures of suicide and self-harm. Phenome-wide association analyses using BPD-PGS confirmed these associations and additionally revealed associations with general medical conditions including obstructive pulmonary disease and diabetes. The present analyses highlight BPD as a polygenic disorder, with the genetic risk showing substantial overlap with psychiatric and physical health conditions.

PMID: 40832388

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