International Borderline Genomics Consortium

Borderline Personality Disorder (BPD) is a mental health condition characterized by pervasive instability in moods, self-image, and behavior, often leading to impulsive actions and unstable relationships. Symptoms include intense episodes of anger, depression, and anxiety that can last from a few hours to days. Research indicates that BPD has a heritability estimate of approximately 46%, suggesting a significant genetic component to the disorder. 
(Skoglund et al., 2019)

Despite this evidence of heritability, comparatively few genomic studies have been conducted to identify molecular markers linked to BPD, especially when compared to other mental disorders. Identifying such markers could lead to more effective treatments and interventions for those affected.

We, the International Borderline Genomics Consortium (IBGC), are a collaborative research network dedicated to uncovering the genetic foundations of BPD. Our work focuses on large-scale genome-wide association studies (GWAS) to identify genetic risk factors linked to BPD and its overlap with other psychiatric conditions.

In our first case-control GWAS, we analyzed data from 998 BPD patients and 1,545 controls. While no single genetic variant reached genome-wide significance, gene-based analyses identified two significant genes: DPYD and PKP4. Our study also revealed a genetic overlap between BPD and other psychiatric disorders, such as bipolar disorder, major depression, and schizophrenia. 
(Witt et al., 2017)

Beyond GWAS, we have explored genetic correlations between BPD and personality traits, finding strong associations with Neuroticism and Openness but not with the other Big Five traits. Additionally, we identified a genetic link between BPD and loneliness, suggesting that individuals with a genetic predisposition to loneliness are more likely to develop BPD. 
(Streit et al., 2022; Schulze et al., 2023)

Our data have also contributed to other GWAS, notably in studies of suicide attempt, where our cohort was part of a meta-analyses that identified genome-wide significant loci associated with suicide attempts. (Mullinhs et al., 2022; Docherty et al., 2024); Additionally, research has explored the shared genetics between BPD and body composition ans glycemic traits (Hübel et al., 2024) as well as thyroid function (Babajida et al., 2024), providing further insights into the complex interplay between genetic factors and BPD. 
 

Building on these findings, we conducted a second, much larger GWAS with data from 13,024 BPD patients and 1,149,467 control participants. This study identified 11 genetic loci associated with BPD, further confirming the disorder’s complex genetic architecture and shared risk factors with multiple psychiatric and somatic conditions. 
(Streit et al., 2024)

We have also extended our research into the investigation of omics markers, such as methylation and gene expression, to better understand the biological mechanisms underlying BPD. Notably, Dr. Fabian Streit, a leading member of our consortium, was awarded a 2023 NARSAD Young Investigator Grant to study epigenome-wide DNA methylation and transcriptome-wide gene expression profiles associated with BPD directly in postmortem brain tissue. This project aims to explore how environmental factors may influence BPD through epigenetic modifications.

If you are interested in working with our data (e.g., summary statistics) or would like to collaborate on future GWAS, please feel free to get in contact with us. We are always open to expanding our network and working together to further advance the understanding of BPD’s genetic basis.

To further explore genetic research across the broader spectrum of personality disorders and connect with a wider community of researchers, we also invite you to visit the Personality Disorders Genomics Group. This working group fosters collaboration, shares findings, and organizes regular meetings focused on advancing the genetics of personality disorders.