Abstract
Borderline personality disorder (BPD) often co-occurs with other health conditions, but the role of genetics vs. environment is unclear. In this multigenerational cohort study using Swedish national registers, the authors quantified the co-aggregation of BPD with other phenotypes in families and estimated the genetic vs. environmental contributions. In a birth cohort of individuals born 1973–2001 and their twins, siblings, cousins, parents, and aunts/uncles, the exposure was BPD in the proband. Odds ratios were estimated for 19 psychiatric, 18 somatic, and seven behavioral/injury outcome phenotypes within individuals and relative pairs. Structural equation modeling was used to estimate genetic, common environmental, and unique environmental contributions to phenotypic associations and genetic correlations (rg). Of the 2.7 million individuals in the birth cohort (mean age at follow-up end = 31.7 years, SD = 9.8, 48.5% female), 24,547 (86% female) were diagnosed with BPD by follow-up end. Relatives of individuals with BPD had increased risk for various psychiatric, somatic, and behavioral phenotypes, except cystic fibrosis. Psychiatric phenotypes showed the strongest phenotypic and genetic correlations, with equal contributions from genetic and unique environmental factors. The pattern varied for somatic phenotypes, which also had weaker correlations. Sleep disorders showed the strongest genetic overlap with BPD (rg = 0.74, 95%CI = 0.39–1.08). Behavioral phenotypes related to BPD symptoms showed strong associations and genetic overlap (e.g., self-harm rg = 0.80, 95%CI = 0.55–1.04), whereas accident-related phenotypes had weaker associations and varied genetic/environmental contributions. BPD co-aggregates with many phenotypes, with psychiatric conditions showing the strongest genetic overlap. These findings guide further research on BPD comorbidity causes and interventions.
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Data availability
The data analyzed in this study are available from Statistics Sweden and The Swedish National Board of Health and Welfare. The Public Access to Information and Secrecy Act in Sweden prohibits publication of individual-level data. Researchers who are interested in replicating our work can, after obtaining ethical approval, apply for data through Statistics Sweden at: https://www.scb.se/en/services/guidance-for-researchers-and-universities/.
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This work was supported by Inge Lehmann Grant number 1133-00034B from the Independent Research Fund Denmark. The Independent Research Fund Denmark had no further role in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; or in the decision to submit the article for publication. Open access funding provided by Karolinska Institute.
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ASMH: conceptualization, methodology, data curation, formal analysis, visualization, writing – original draft, writing – review & editing. KLM: conceptualization, writing – review & editing, funding acquisition. JCPD: writing – review & editing. BJV: writing – review & editing. ZC: resources, writing – review & editing. BMD: resources, writing – review & editing. PL: resources, writing – review & editing, supervision. RKH: conceptualization, methodology, formal analysis, writing – review & editing, resources. IB: conceptualization, methodology, writing – review & editing, resources, funding acquisition. The corresponding authors confirm that all co-authors substantially contributed to either the conception/design of the work or the acquisition/analysis/interpretation of data, critically reviewed the work for important intellectual content, and approved the final version to be published. In addition, all co-authors will strive to investigate and resolve any questions related to the accuracy/integrity of the work should these arise.
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BJV is a member of the advisory board of Allelica. ZC has previously received speaker fees from Takeda Pharmaceuticals. ASMH, KLM, JCPD, PL, BMD, RKH, and IB report no financial relationships with commercial interests or potential conflicts of interest.
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This study was approved by the Swedish Ethical Review Authority (reference number 2020-06540). Informed consent is not required for pseudonymized register-based research according to the Swedish law. All analyses were performed in accordance with the relevant guidelines and regulations.
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Hall, A.S.M., Musliner, K.L., Debost, JC.P. et al. Borderline personality disorder and other psychiatric, somatic, and behavioral conditions: a nationwide family study. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-04001-w
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DOI: https://doi.org/10.1038/s41398-026-04001-w


