Evidence for a shared genetic contribution to loneliness and Borderline Personality Disorder

Background 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. Methods 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; sample 1: 998 BPD, 1545 HC; sample 2: 187 BPD, 261 HC). In sample 2, we examined associations of loneliness-PGS with reported loneliness, and whether the loneliness-PGS influenced the association between childhood maltreatment and loneliness. Results We found a genetic correlation between the GWAS of loneliness and BPD, a positive association of loneliness-PGS with BPD case-control status, and a positive association between loneliness-PGS and loneliness across groups. The loneliness-PGS did not moderate the association between childhood maltreatment and loneliness in BPD. Conclusion 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, indicating that genetic predisposition for loneliness might contribute to BPD risk. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the German Research Foundation (KFO-256 and GRK2350/3 - 324164820). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committees of the medical faculty Mannheim of Heidelberg University, medical faculty Ludwig-Maximilians University, Landesaerztekammer Rheinland-Pfalz and Charite Berlin gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets presented in this article are not readily available because according to European law (GDPR), data containing potentially identifying or sensitive patient information are restricted; our data involving clinical participants are not freely available in the article, Supplementary Material, or in a public repository. Data are available upon reasonable request to the authors.