Largest genetic study of borderline personality disorder uncovers first robust risk clues

The largest genetic study of borderline personality disorder (BPD) to date has identified the first robust evidence that inherited variants raise the risk of the condition, according to findings published in *Nature Genetics* on 20 July ( The genome-wide association study (GWAS) pinpointed 11 locations in the human genome associated with BPD, including nine functional genes thought to be linked to the disorder. Researchers led by Fabian Streit, a psychologist at the Central Institute of Mental Health in Mannheim, Germany, combined data from 27 studies encompassing 12,339 people with BPD and more than one million unaffected individuals. Six genomic sites remained significant in an independent replication involving 685 people with BPD and 107,750 controls; five further loci emerged when the analyses were combined, though those still require replication in separate studies ( The team estimated that the newly found variants account for roughly 17% of the inherited risk of BPD. That underscores that "genetics is pretty important, but it can never explain or paint the whole picture," Streit said, noting that family and twin studies have previously put the heritability of the condition between 46% and 69%. BPD, marked by long-term emotional instability, distorted perceptions and turbulent relationships, affects up to 2% of people in Western countries and is diagnosed about three times more often in women. Andrew McIntosh, a psychiatrist at the University of Edinburgh who studies psychiatric genetics, called the work "an extraordinary step up from where we've been previously, with virtually no research being conducted on the condition at scale," adding that genetic approaches now look "fruitful" as they have been for schizophrenia, depression and bipolar disorder. Only one GWAS of BPD had been published before, and it found no significant variants — leaving the condition "understudied from this perspective of psychiatric genetics," Streit said. The new analysis, drawing on biobanks and clinical cohorts of European ancestry, is expected to help guide biological research and, eventually, approaches to treatment.