Evidence for a shared genetic contribution to loneliness and borderline personality disorder

Anna Schulze; Fabian Streit; Lea Zillich; Swapnil Awasthi; Alisha S M Hall; Martin Jungkunz; Nikolaus Kleindienst; Josef Frank; Cornelia E Schwarze; Norbert Dahmen; Björn H Schott; Markus Nöthen; Arian Mobascher; Dan Rujescu; Klaus Lieb; Stefan Roepke; Sabine C Herpertz; Christian Schmahl; Martin Bohus; Stephan Ripke; Marcella Rietschel; Stefanie Lis; Stephanie Witt

doi:10.1038/s41398-023-02705-x

Evidence for a shared genetic contribution to loneliness and borderline personality disorder

Transl Psychiatry. 2023 Dec 18;13(1):398. doi: 10.1038/s41398-023-02705-x.

Authors

Anna Schulze^#¹, Fabian Streit^#², Lea Zillich², Swapnil Awasthi^{3

4}, Alisha S M Hall^{2

5

6}, Martin Jungkunz⁷, Nikolaus Kleindienst⁸, Josef Frank², Cornelia E Schwarze⁹, Norbert Dahmen¹⁰, Björn H Schott^{11

12

13}, Markus Nöthen¹⁴, Arian Mobascher¹⁵, Dan Rujescu¹⁶, Klaus Lieb¹⁰, Stefan Roepke¹⁷, Sabine C Herpertz¹⁸, Christian Schmahl⁸, Martin Bohus^{8

19}, Stephan Ripke^{3

4

20}, Marcella Rietschel², Stefanie Lis^#^{21

8}, Stephanie Witt^#²

Affiliations

¹ Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. anna.schulze@zi-mannheim.de.
² Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
⁵ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁶ Department of Affective Disorders, Aarhus University Hospital-Psychiatry, Aarhus, Denmark.
⁷ National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg University, Medical Faculty Heidelberg, Department of Medical Oncology, Section Translational Medical Ethics, Heidelberg, Germany.
⁸ Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁹ Department of Psychology, Developmental and Biological Psychology Unit, Heidelberg University, Heidelberg, Germany.
¹⁰ Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
¹¹ Leibniz Institute for Neurobiology, Magdeburg, Germany.
¹² Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
¹³ German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
¹⁴ Institute of Human Genetics, University Hospital Bonn, Bonn, Germany.
¹⁵ Department of Psychiatry and Psychotherapy, St. Elisabeth Krankenhaus Lahnstein, Lahnstein, Germany.
¹⁶ Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
¹⁷ Department of Psychiatry and Neuroscience, Charité - Universitätsmedizin Berlin, Berlin, Germany.
¹⁸ Department of General Psychiatry, Center for Psychosocial Medicine, Medical Faculty, Heidelberg University, Heidelberg, Germany.
¹⁹ Department of Clinical Psychology, Ruhr University Bochum, Bochum, Germany.
²⁰ Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Analytic and Translational Genetics Unit, Boston, MA, USA.
²¹ Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

^# Contributed equally.

Abstract

Loneliness, influenced by genetic and environmental factors such as childhood maltreatment, is one aspect of interpersonal dysfunction in Borderline Personality Disorder (BPD). Numerous studies link loneliness and BPD and twin studies indicate a genetic contribution to this association. The aim of our study was to investigate whether genetic predisposition for loneliness and BPD risk overlap and whether genetic risk for loneliness contributes to higher loneliness reported by BPD patients, using genome-wide genotype data. We assessed the genetic correlation of genome-wide association studies (GWAS) of loneliness and BPD using linkage disequilibrium score regression and tested whether a polygenic score for loneliness (loneliness-PGS) was associated with case-control status in two independent genotyped samples of BPD patients and healthy controls (HC; Witt2017-sample: 998 BPD, 1545 HC; KFO-sample: 187 BPD, 261 HC). In the KFO-sample, we examined associations of loneliness-PGS with reported loneliness, and whether the loneliness-PGS influenced the association between childhood maltreatment and loneliness. We found a genetic correlation between the GWAS of loneliness and BPD in the Witt2017-sample (rg = 0.23, p = 0.015), a positive association of loneliness-PGS with BPD case-control status (Witt2017-sample: NkR² = 2.3%, p = 2.7*10^-12; KFO-sample: NkR² = 6.6%, p = 4.4*10^-6), and a positive association between loneliness-PGS and loneliness across patient and control groups in the KFO-sample (β = 0.186, p = 0.002). The loneliness-PGS did not moderate the association between childhood maltreatment and loneliness in BPD. Our study is the first to use genome-wide genotype data to show that the genetic factors underlying variation in loneliness in the general population and the risk for BPD overlap. The loneliness-PGS was associated with reported loneliness. Further research is needed to investigate which genetic mechanisms and pathways are involved in this association and whether a genetic predisposition for loneliness contributes to BPD risk.

MeSH terms

Borderline Personality Disorder* / genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Loneliness*

Abstract

MeSH terms

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