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

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 BatzlerMichael 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, Thomas F Hansen, Henrik Hjalgrim, Bitten Aagaard, Anders Jorgensen, Christina Mikkelsen, Sisse R Ostrowski, Ole Bv Pedersen, Michael Schwinn, Erik Sørensen, Jacob Træholt, Henrik Ullum, Thomas Werge, DBDS Genomic Consortium

Abstract

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.

OriginalsprogEngelsk
DOI
StatusE-pub ahead of print - 12 aug. 2025
NavnmedRxiv : the preprint server for health sciences

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