Borderline personality disorder and the big five: molecular genetic analyses indicate shared genetic architecture with neuroticism and openness

Abstract

Both environmental (e.g. interpersonal traumatization during childhood and adolescence) and genetic factors may contribute to the development of Borderline Personality Disorder (BPD). Twin studies assessing borderline personality symptoms/features in the general population indicate that genetic factors underlying these symptoms/features are shared in part with the personality traits of the Five Factor Model (FFM) of personality—the “Big Five”. In the present study, the genetic overlap of BPD with the Big Five -Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism- was assessed. Linkage disequilibrium score regression was used to calculate genetic correlations between a genome-wide association study (GWAS) in central European populations on BPD (N = 2543) and GWAS on the Big Five (N = 76,551–122,886, Neuroticism N = 390,278). Polygenic scores (PGS) were calculated to test the association of the genetic disposition for the personality traits with BPD case-control status. Significant positive genetic correlations of BPD were found with Neuroticism (rg = 0.34, p = 6.3*10−5) and Openness (rg = 0.24, p = 0.036), but not with the other personality traits (all | rg | <0.14, all p > 0.30). A cluster and item-level analysis showed positive genetic correlations of BPD with the Neuroticism clusters “Depressed Affect” and “Worry”, and with a broad range of Neuroticism items (N = 348,219–376,352). PGS analyses confirmed the genetic correlations, and found an independent contribution of the personality traits to BPD risk. The observed associations indicate a partially shared genetic background of BPD and the personality traits Neuroticism and Openness. Larger GWAS of BPD and the “Big Five” are needed to further explore the role of personality traits in the etiology of BPD.

Treating Depression in Patients with Borderline Personality Disorder: Clinical Clues on the Use of Antidepressants

“…Recently, different genomewide association studies (GWAS) have been performed, in order to study genetical association of the "Big Five" factors of FFM with PDs in general population. BPD was found closely associated with personality traits of neuroticism and openness [43], and, more interestingly, it was reported to share positive genetic correlations with MDD, Bipolar Disorder and Schizophrenia [44]. As abovementioned, BPD represents a unique construct intermingling specific personality traits, such as disturbed relatedness, behavioral and emotional dysregulation.…”

Evidence for a shared genetic contribution to loneliness and Borderline Personality Disorder

“…For the present analyses, PGS were calculated based on an updated quality control and imputation procedure, which has been described in detail in Streit et al (2022). Subjects were genotyped using Illumina Infinium PsychArray-24 Bead Chips (Illumina, San Diego, CA, USA).…”

“…comparing BPD patients diagnosed using established diagnostic systems to controls, has been performed which did not identify associated single variants but indicated significant gene-based associations in the genes DPYD and PKP4 (Witt et al, 2017). BPD was found to have positive genetic correlations with major depression, bipolar disorder, and schizophrenia (Witt et al, 2017) as well as with the personality traits neuroticism and, to a lesser degree, openness to experience (Streit et al, 2022). At the same time, a recent GWAS in the UK Biobank identified 15 genome-wide significant loci associated with loneliness (Day et al, 2018), measured by three variables assessing the feeling of loneliness, the frequency of interacting with others and the possibility to confide in others.…”

Relationship of DRD5 and MAO‐B VNTR polymorphisms with paranoid and antisocial personality disorders in polydrug users

“…The possibility that maladaptive personality traits may be related to polygenic inheritance could correspond to an increased vulnerability to developing a PD (Lo et al, 2017). Indeed, a recent study of GWAS found a partially shared genetic background for borderline personality disorder (BPD) and neuroticism and openness (Streit et al, 2022).…”

“…The possibility that maladaptive personality traits may be related to polygenic inheritance could correspond to an increased vulnerability to developing a PD (Lo et al, 2017). Indeed, a recent study of GWAS found a partially shared genetic background for borderline personality disorder (BPD) and neuroticism and openness (Streit et al, 2022). Epidemiological studies carried out in families, twins and adoptions have proven to be more effective in determining the heritability of certain traits (Mateu et al, 2008).…”