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Genome-wide Association Study of Borderline Personality Disorder Reveals Genetic Overlap with Bipolar Disorder, Major Depression and Schizophrenia

Witt, S.H. and Streit, F. and Jungkunz, M. and Frank, J. and Awasthi, S. and Reinbold, C.S. and Treutlein, J. and Degenhardt, F. and Forstner, A.J. and Heilmann-Heimbach, S. and Dietl, L and Schwarze, CE and Schendel, D and Stohmaier, J and Jones, Lisa and Gordon-Smith, Katherine and Knott, Sarah and Perry, Amy and Bipolar Disorders Working Group of the PGC, and Major Depressive Disorder Working Group of the PGC, and Schizophrenia Working Group of the PGC, (2017) Genome-wide Association Study of Borderline Personality Disorder Reveals Genetic Overlap with Bipolar Disorder, Major Depression and Schizophrenia. Translational Psychiatry, 7. ISSN 2158-3188

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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 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). 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=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe 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.

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Uncontrolled Keywords: genome wide association study, borderline personality disorder, bipolar disorder, major depression, schizophrenia
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Academic Departments > Institute of Health and Society
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Copyright Info: Open Access article
Depositing User: Katherine Gordon-Smith
Date Deposited: 22 Jun 2017 08:30
Last Modified: 22 Jun 2017 08:31
URI: https://eprints.worc.ac.uk/id/eprint/5617

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