Autor:innen:
Fabian Streit, Mannheim (Germany)
Swapnil Awasthi, Berlin (Germany)
IBGC International Borderline Genomics Consortium, Mannheim (Germany)
Marcella Rietschel, Mannheim (Germany)
Stephan Ripke, Berlin (Germany)
Stephanie Witt, Mannheim (Germany)
Environmental influences such as early trauma and stress are well-established risk factors contributing to the development of Borderline Personality Disorder (BPD). Twin and family studies indicate a substantial contribution of genetic factors. Previously, we reported the first genome-wide association study (GWAS) which systematically investigated the genetic variation contributing to BPD (i.e. Witt et al. 2017, n cases = 998).
We now carried out the so far largest genome-wide association study (GWAS) on BPD, consisting of 2,660 cases and 4,593 controls from clinical studies, and 4,050 cases and 561,182 controls from cohort/biobank studies providing summary statistics (total n: cases = 6,710, controls = 565,775).
There were no variants associated with BPD reaching genome-wide significance. Strong genetic correlations were observed between the previous (Witt et al, 2017) and current clinical samples (rg = .90, p = .0018) and between the clinical and cohort/biobank samples (rg = .89; p = 8.06*10-8). We replicate the previously reported genetic overlap with schizophrenia (rg = .34, p = 2.43*10-16), bipolar disorder (rg = .28, p = 2.40*10-7) and depression (rg = .61, p = 1.21*10-11). Polygenic risk scores based on the cohort/biobank studies predicted up to 1.5% of the variance in case-control status in the clinical studies. We observed positive genetic correlations with smoking, somatic disorders, mood swings, risk-taking, neuroticism, pain phenotypes and material deprivation and negative correlations with educational attainment and physical activity. Notably, positive genetic correlations were also observed with comorbid psychiatric disorders such as ADHD and post-traumatic stress disorder as well as with self-reported childhood maltreatment (all rg: p < 1*10-4).
The present GWAS, albeit small in comparison to other current psychiatric GWAS, represents a substantial progress for the investigation of the etiology of BPD using molecular genetic methods in more detail.