Streit Fabian, Awasthi Swapnil, Hall Alisha Sm, Braun Alice, Niarchou Maria, Marouli Eirini, Babajide Oladapo, Frank Josef, Zillich Lea, Callies Carolin M, Avetyan Diana, Zillich Eric, Naamanka Joonas, Gonzalez Jean, Harder Arvid, Lu Yi, 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, de Sá Diana S Ferreira, 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, Oddsson Asmundur, Ostrowski Sisse R, Palviainen Teemu, Pedersen Ole Bv, Pedersen Geir, Quinn Liam, Reinhard Matthias A, Ruths Florian A, Schott Björn H, Schredl Michael, Schwarz Emanuel, Schwarze Cornelia E, Schwinn Michael, Send Tabea, Sigurdsson Engilbert, Simon-Keller Katja, Skuladottir Astros T, 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, 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, Sanchez-Roige Sandra, 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
Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
medRxiv. 2025 Aug 12:2024.11.12.24316957. doi: 10.1101/2024.11.12.24316957.
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.
我们开展了迄今为止最大规模的边缘性人格障碍（BPD）全基因组荟萃分析，发现样本包括12339例病例和1041717例对照，复制研究样本包括685例病例和107750例对照（所有参与者均为欧洲血统）。我们在基于基因的分析中确定了11个独立的相关基因组位点和9个风险基因。我们观察到单核苷酸多态性（SNP）遗传度为17.3%，推导的多基因评分（PGS）在易感性量表上预测了BPD中4.6%的表型变异。BPD与创伤后应激障碍、抑郁症、注意力缺陷多动障碍、反社会行为以及自杀和自我伤害测量的全基因组关联研究（GWAS）显示出最强的正遗传相关性。使用BPD-PGS进行的全表型组关联分析证实了这些关联，此外还揭示了与包括阻塞性肺病和糖尿病在内的一般医疗状况的关联。目前的分析突出了BPD作为一种多基因疾病，其遗传风险与精神和身体健康状况存在大量重叠。
