Researchers have identified the first evidence of genetic risk factors associated with borderline personality disorder (BPD).

The analysis, published in Nature genetics July 20¹is the largest genome-wide association study (GWAS) of the disease to date. He identified 11 associated locations (or loci) in the human genome, and within or near these broad areas were nine functional genes that appear to be related to BPD.

The condition affects up to 2% of people in Western countries, and women are around three times more likely to be diagnosed with BPD than men.

Genetic and environmental risk factors are thought to contribute to the risk of developing the condition. However, “it has been little studied from this perspective of psychiatric genetics,” says study co-author Fabian Streit, a psychologist at the Central Institute of Mental Health in Mannheim, Germany. Only one GWAS of the disorder had been published before and did not identify any significant variants associated with the condition.².

The latest findings suggest that “genetic approaches are going to be fruitful in the study of this disorder, as they have been in other disorders such as schizophrenia, depression and bipolar disorder,” says Andrew McIntosh, a psychiatrist who studies the genetics of such disorders at the University of Edinburgh, United Kingdom.

It is “an extraordinary step from where we were previously, where practically no research has been done on this disease at scale,” he adds.

Genetic factors

BPD is diagnosed on the basis of long-term patterns of emotional instability, cognitive and perceptual distortions, and unstable relationships with others. People with this disorder often “have acute periods of crisis, which can sometimes lead to hospital admission,” explains McIntosh.

These factors have made it difficult to enroll people with BPD in studies, he adds.

In the current work, Streit and colleagues combined data from a total of 27 studies that recruited people with BPD or that analyzed genetic and health records from biobanks. All participants were of European descent.

Huge genetic study reveals hidden links between psychiatric illnesses

The team first examined more than six million genetic markers in two groups of people: 12,339 people with BPD and more than one million people who did not have the disease. The researchers found six sites in the genome that contained genetic variants associated with BPD. These variants remained significant in a replication analysis involving 685 people with BPD and 107,750 people without the disorder.

When the researchers combined both analyses, they identified five more loci in the genome that showed an association with BPD. These “five variants have yet to be replicated in independent studies,” McIntosh notes.

Streit and colleagues also estimated that newly identified genetic variants account for about 17% of the inherited risk of BPD. This suggests that “it’s a disorder where genetics are quite important, but can never explain or paint the full picture,” Streit says.

Previous family and twin studies.³,⁴ have suggested that the heritability of BPD is between 46% and 69%.