Specific genetic variants can be linked to a particular condition by analysing the genomes of large groups of people with and without the disorder.Credit: Gregory Adams/Getty
Researchers have identified the first evidence of genetic risk factors associated with borderline personality disorder (BPD).
The analysis, published in Nature Genetics on 20 July1, is the largest genome-wide association study (GWAS) of the condition so far. It identified 11 associated locations (or loci) in the human genome, and within or near these broad areas were nine functional genes that seem to be linked 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 are men.
Genetic and environmental risk factors are thought to contribute to the risk of developing the condition. Yet, it has “been understudied 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 it did not identify any significant variants associated with the condition2.
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, UK.
It is “an extraordinary step up from where we’ve been previously, with virtually no research being conducted on the condition 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 the disorder often “have acute periods of crisis, which can sometimes lead to hospital admission,” explains McIntosh.
These factors have made it challenging to enrol people who have BPD in studies, he adds.
In the current work, Streit and his colleagues combined data from a total of 27 studies that recruited people with BPD or that analysed genetic and health records from biobanks. All participants were of European ancestry.
Huge genetic study reveals hidden links between psychiatric conditions
The team first examined more than six million genetic markers in two groups of people: 12,339 individuals with BPD and more than one million people who did not have the condition. The researchers found six sites on the genome that contained genetic variants that were 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 further loci on the genome that showed an association with BPD. These “five variants are still to be replicated in independent studies,” notes McIntosh.
Streit and his colleagues also estimated that the newly identified genetic variants account for about 17% of the inherited risk of BPD. This suggests it “is a disorder where genetics is pretty important, but it can never explain or paint the whole picture”, notes Streit.
Previous family and twin studies3,4 have suggested that the heritability of BPD is between 46% and 69%.
