Genome-wide association study of borderline personality disorder identifies six loci and highlights shared risk with mental and somatic disorders
Authors: Streit Fabian , Awasthi Swapnil , Hall Alisha SM , Niarchou Maria , Marouli Eirini , Babajide Oladapo , Braun Alice , Frank Josef , Zillich Lea , Callies Carolin , Avetyan Diana , Zillich Eric , Naamanka Joonas , Aherrahrou Zouhair , Ahmad Zain-Ul-Abideen , Ask Helga , Batzler Anthony , Benros Michael E , Brand-de Wilde Odette M , Brunak Søren , Bruun Mie T , Christoffersen Lea AN , Colodro-Conde Lucía , Coombes Brandon J , Corfield Elizabeth C , Dahmen Norbert , Didriksen Maria , Dinh Khoa M , Djurovic Srdjan , Dowsett Joseph , Drange Ole Kristian , Dukal Helene , Edelmann Susanne , Erikstrup Christian , Espinola Mariana K , Fassbinder Eva , Faucon Annika , Ferreira de Sá Diana S , Foo Jerome C , Gilles Maria , Gutiérrez-Zotes Alfonso , Hansen Thomas F , Haraldsson Magnus , Harper R. Patrick , Havdahl Alexandra , Heilbronner Urs , Herms Stefan , Hjalgrim Henrik , Hübel Christopher , Jacob Gitta A , Aagaard Bitten , Jorgensen Anders , Jungkunz Martin , Kleindienst Nikolaus , Knoblich Nora , Koglin Stefanie , Kraft Julia , Krebs Kristi , Lee Christopher W , Lin Yuhao , Lis Stefanie , Lisoway Amanda , Malogiannis Ioannis A , Martinsen Amy , Maslahati Tolou , Merz Katharina , Meyer-Lindenberg Andreas , Mikkelsen Susan , Mikkelsen Christina , Mobascher Arian , Muntané Gerard , Oddson Asmundur , Ostrowski Sisse R , Palviainen Teemu , Pedersen Ole BV , Pedersen Geir , Quinn Liam , Reinhard Matthias A , Ruths Florian A , Sanchez-Roige Sandra , Schott Björn H , Schredl Michael , Schwarz Emanuel , Schwarze Cornelia E , Schwinn Michael , Send Tabea , Sigurdsson Engilbert , Simon-Keller Katja , Soler Joaquim , Sonley Anne , Sørensen Erik , Stefansson Hreinn , Straub Peter , Suvisaari Jaana , Tesli Martin , Træholt Jacob , Ullum Henrik , Völker Maja P , Walters G Bragi , Wang Rujia , Witt Christian C , Zarbock Gerhard , Zill Peter , Zwart John-Anker ,   Estonian Biobank Research Team,   the GLAD Study,   HUNT All-In Psychiatry, Andreassen Ole A , Arntz Arnoud , Biernacka Joanna M , Bohus Martin , Breen Gerome , Chapman Alexander L , Cichon Sven , Davis Lea K , Deuschle Michael , Euler Sebastian , Herpertz Sabine C , Hummelen Benjamin , Jobst Andrea , Kaprio Jaakko , Kennedy James L , Lehto Kelli , Lieb Klaus , Martorell Lourdes , McMain Shelley , Musil Richard , Nieratschker Vanessa , Nöthen Markus M , Padberg Frank , Palotie Aarno , Pascual Juan C , Perroud Nader , Ramos-Quiroga Josep A , Reichborn-Kjennerud Ted , Ribases Marta , Roepke Stefan , Rujescu Dan , Schilling Claudia , Schmahl Christian , Stefansson Kari , Thorgeirsson Thorgeir E , Turecki Gustavo , Vilella Elisabet , Werge Thomas , Winsvold Bendik S , Wrege Johannes , Rietschel Marcella , Ripke Stephan , Witt Stephanie H 
Published: November 2024

Environmental and genetic risk factors contribute to the development of borderline personality disorder (BPD). We conducted the largest GWAS of BPD to date, meta-analyzing data from 12,339 cases and 1,041,717 controls of European ancestry, and identified six 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 case-control status. 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 revealed associations of BPD risk with general medical conditions including obstructive pulmonary disease and diabetes. The present genetic analyses highlight BPD as a polygenic disorder, with the genetic risk showing substantial overlap with psychiatric and physical health conditions.