2 research outputs found
Genome-wide association study of borderline personality disorder reveals genetic overlap with the bipolar disorder, schizophrenia and major depression
Borderline personality disorder (BOR) is determined by environmental and genetic factors,
and characterized by affective instability and impulsivity, diagnostic symptoms also observed
in manic phases of Bipolar Disorder (BIP). Up to 20% of BIP patients show comorbidity with
BOR. This report describes the first case-control genome-wide association study (GWAS) of
BOR, performed in one of the largest BOR patient samples worldwide. The focus of our
analysis was: (i) to detect genes and gene-sets involved in BOR; and (ii) to investigate the
genetic overlap with BIP. As there is considerable genetic overlap between BIP, Major
Depression (MDD) and Schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we
also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests,and gene-set-analyses were performed in 998 BOR patients and 1,545 controls. LD score
regression was used to detect genetic overlap between BOR and these disorders. Single
marker analysis revealed no significant association after correction for multiple testing. Genebased
analysis yielded two significant genes: DPYD (p=4.42x10-7) and PKP4 (p=8.67x10-7);
and gene-set-analysis yielded a significant finding for exocytosis (GO:0006887, pFDR=0.019).
Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most
notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28
[p=2.99x10-3]), SCZ (rg=0.34 [p=4.37x10-5]), and MDD (rg=0.57 [p=1.04x10-3]). Our study is
the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level.
Whether this is confined to transdiagnostic clinical symptoms should be examined in future
studies
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe