A landmark genetic study is providing new insights into the biology of one of psychiatry’s most challenging conditions: borderline personality disorder.
Gathering data from more than 12,000 people of European ancestry with borderline personality disorder and over 1 million controls, an international group of researchers under the lead of the Central Institute of Mental Health, Mannheim confirmed findings from previous twin and family studies regarding the role of genetics in the etiology of borderline personality disorder.
“Twin and family studies have already shown that genetics play a substantial role in the etiology of [borderline personality disorder], and our study confirms this using a different approach,” explains lead researcher Fabian Streit in an interview with HealthStack. “Our approach may also be easier to understand, as the genetic risk has been put in terms of actual genetic risk variants now identified. While I am sure that most clinicians would acknowledge that individuals differ in their genetic/biological vulnerability, this is not the focus of established therapies, which rightfully focus on modifiable factors.”
The findings provide strong genetic evidence that borderline personality disorder is a highly polygenic condition. This means multiple genetic variants rather than a single disease-causing mutation influence the risk.
Decoding Borderline Personality As A Polygenic Disorder
Researchers identified 11 independent genomic loci associated with borderline personality disorder and nine risk genes through gene-based analyses. The findings showed that investigated genetic variants account for about 17.3% of inherited susceptibility to borderline personality disorder.
They also found substantial genetic overlap between borderline personality disorder and several psychiatric conditions, including post-traumatic stress disorder, major depression and attention-deficit/hyperactivity disorder.
Streit emphasized that these findings do not diminish the role of environmental factors. Streit explains those factors play a key role in the development of the disorder.
“We acknowledge the importance of environmental factors,” says Streit. “[We] do not see our results as being in conflict with any previous work showing the role of trauma in increasing risk for borderline personality disorder.”
Individuals with higher polygenic risk for borderline personality disorder were more likely to have certain physical health conditions, according to the findings. These conditions include chronic obstructive pulmonary disease, type 2 diabetes, hypertension and pain-related conditions.
Despite identifying multiple genetic loci and risk genes, the study did not identify clear therapeutic targets. The researchers noted that none of the prioritized genes currently correspond to established drug targets in public databases.
Strengthening Scientific Evidence For Borderline Personality Disorder
Borderline personality disorder is a highly stigmatized and complex psychiatric disorder that carries a significant risk of self-harm and suicide. The condition is diagnosed more often in women, who account for nearly 75% of people being treated for borderline personality disorder in mental healthcare settings.
Researchers believe the study helps move the field beyond symptom-based descriptions toward a better understanding of the biological mechanisms involved. Key study contributor Alisha Hall tells HealthStack, she hopes the new findings will push clinicians to incorporate biological vulnerability alongside environmental influences when treating people.
“We hope that clinicians will continue to think about the component of biological vulnerability and talk about it with people getting treated for [borderline personality disorder] to understand why they developed the disorder,” Hall shares.
Translating Results To Clinical Applications
The results of the study identified genetic variants associated with borderline personality disorder. However, researchers note that the path to clinical application is long.
“The path from the first genetic findings to clinical application is long and winding, and we are not there yet,” explains Hall. “You could say that our results have revealed the tip of the iceberg. We need studies in even bigger — and more diverse — samples to be able to precisely identify and understand the genetic variants involved in [borderline personality disorder].”
Dialectical behavior therapy remains a leading evidence-based treatment for borderline personality disorder because there are no U.S. Food and Drug Administration-approved medications indicated for the condition. Clinicians often manage borderline personality disorder alongside complex psychiatric conditions, including depression, post-traumatic stress disorder and substance use disorders.
Both Streit and Hall hope the study could be used as a basis for future studies in the field.
“Our study will hopefully inspire more research in the field,” Streit says. “For example, polygenic scores calculated with the results can be used as a research tool to investigate pathways from genetic risk to actually developing [borderline personality disorder]. But, in the future, given larger samples, our results might be able to help identify drug candidates for [borderline personality disorder] treatment.
Researchers Caution The Sample Diversity May Affect Findings
This historic study offers new insight into a disorder that has long remained poorly understood. However, Streit says the findings should be interpreted carefully based on the selected participant pool.
“We know from previous studies that the signals we detect in European-ancestry samples don’t translate as well to samples of other genetic ancestries,” explains Hall. “For example, the previously mentioned polygenic scores are substantially less informative when applied in samples of other ancestries. This is largely due to differences in the frequency of and correlations between genetic variants across ancestries. Although differences in culture and healthcare system can also play a role.”
The research team decided to limit the participant sample to only those with European ancestry for various reasons. Some of those reasons include data availability, and the need to control population stratification and risk of false genetic associations. Streit shares he hopes future studies can help improve the applicability of results across ethnic groups.
“The best way to address this limitation is to include samples of other genetic ancestries in our studies,” Streit says. “For other mental disorders, like Major Depressive Disorder, there has been much more progress in including diverse genetic datasets. However, we are confident that we can change this in the future.”
The Researchers Are Actively Trying To Expand The Study
Streit says he and the team are already looking forward to expanding the study results.
“We are already in contact with the data owners of some samples with a more diverse representation of genetic ancestries for the next iteration of our study, and we would of course be happy to collaborate with more researchers on this front,” Streit says. “In addition, we are working on including data from existing biobanks that have more individuals of non-European ancestry.”
However, he notes biobanks remain underrepresented in populations of non-European ancestry. This lack of data continues to limit the diversity and generalizability of biomedical research.
“Worldwide, non-European ancestries are still vastly underrepresented in biobanks and genetic studies on mental health,” Hall says, adding, “This will hopefully improve in the coming years.”
Streit says he and the team made the results of their analysis publicly available online for the international research community. He adds they hope their findings will encourage further genetic and biological research into borderline personality disorder and help deepen disease etiology.
“We hope our research will stimulate genetic/biological research on [borderline personality disorder], diving deeper into the biology of the associated associations,” Streit explains, adding they hope fellow researchers begin to look at the disorder beyond the binary diagnosis. “There are already some projects ongoing, and we are excited to see the results soon.”
