Genome-wide analyses of borderline personality features

Area of Science:

• Psychiatry
• Genetics
• Neuroscience

Background:

• Heritability of borderline personality (BP) features is well-established through twin and family studies.
• Previous research indicates a genetic component to BP traits, but specific genetic underpinnings require further investigation.

Purpose of the Study:

• To estimate the heritability of BP features using genome-wide single-nucleotide polymorphism (SNP) data.
• To conduct the first genome-wide association study (GWAS) for BP features and identify associated genetic loci.
• To explore the genetic heterogeneity across different facets of BP features.

Main Methods:

• Utilized data from two large Dutch cohorts (N=7125) from the Netherlands Twin Register and The Netherlands Study of Depression and Anxiety.
• Calculated heritability of the Personality Assessment Inventory Borderline Features Scale (PAI-BOR) total score and subscales using genome-wide SNP data.
• Performed a GWAS for BP features and validated findings in an independent cohort (N=1301).

Main Results:

• Heritability of the PAI-BOR total score was estimated at 23%.
• Genetic variance was significantly higher for affect instability items (42.7%) compared to self-harm, negative relations, and identity problems.
• A promising GWAS signal was identified on chromosome 5, corresponding to SERINC5, a gene involved in myelination, and confirmed in an independent cohort.
• SNP associations with SERINC5 varied across PAI-BOR items and were primarily observed in individuals with higher BP scores.

Conclusions:

• Genome-wide analyses of BP features demonstrate significant heritability and highlight genetic heterogeneity across symptom clusters.
• SERINC5 emerges as a potential genetic locus associated with BP features, particularly affect instability, suggesting a role for myelination.
• Future GWAS studies on BP features should consider phenotypic and genetic heterogeneity for enhanced discovery.