Genome-wide association study of borderline personality disorder reveals genetic overlap with the bipolar disorder, schizophrenia and major depression

Witt, Stephanie H, Streit, Fabian, Jungkunz, Martin, Frank, Josef, Awasthi, Swapnil, Reinbold, Céline S, Treutlein, Jens, Degenhardt, Franziska, Forstner, Andreas J, Heilmann-Heimbach, Stefanie, Dietl, Lydie, Schwarze, Cornelia E, Schende, Darja l, Strohmaier, Jana, Bethell, Andrew, Craddock, Nicholas ORCID: https://orcid.org/0000-0003-2171-0610, Di Florio, Arianna ORCID: https://orcid.org/0000-0003-0338-2748, Forty, Elizabeth, Fraser, Christine, Hamshere, Marian L. ORCID: https://orcid.org/0000-0002-8990-0958, Holmans, Peter ORCID: https://orcid.org/0000-0003-0870-9412, Jones, Ian ORCID: https://orcid.org/0000-0001-5821-5889, Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, O'Donovan, Michael C ORCID: https://orcid.org/0000-0001-7073-2379 and Owen, Michael J ORCID: https://orcid.org/0000-0003-4798-0862 2017. Genome-wide association study of borderline personality disorder reveals genetic overlap with the bipolar disorder, schizophrenia and major depression. Translational Psychiatry 7 , e1155.

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Nature Publishing Group
ISSN:	2158-3188
Date of First Compliant Deposit:	18 April 2017
Date of Acceptance:	10 April 2017
Last Modified:	06 Nov 2024 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/99919

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