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

Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorders Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)e1155
JournalTranslational Psychiatry
Volume7
Issue number6
DOIs
StatePublished - Jun 20 2017
Externally publishedYes

Fingerprint

Borderline Personality Disorder
Genome-Wide Association Study
Bipolar Disorder
Schizophrenia
Depression
Genes
Exocytosis
Comorbidity
Impulsive Behavior
Linkage Disequilibrium

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorders Working Group of the Psychiatric Genomics Consortium, & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2017). Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia. Translational Psychiatry, 7(6), e1155. https://doi.org/10.1038/tp.2017.115

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia. / Schizophrenia Working Group of the Psychiatric Genomics Consortium; Bipolar Disorders Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Translational Psychiatry, Vol. 7, No. 6, 20.06.2017, p. e1155.

Research output: Contribution to journalArticle

Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorders Working Group of the Psychiatric Genomics Consortium & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2017, 'Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia', Translational Psychiatry, vol. 7, no. 6, pp. e1155. https://doi.org/10.1038/tp.2017.115
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorders Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia. Translational Psychiatry. 2017 Jun 20;7(6):e1155. https://doi.org/10.1038/tp.2017.115
Schizophrenia Working Group of the Psychiatric Genomics Consortium ; Bipolar Disorders Working Group of the Psychiatric Genomics Consortium ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. / Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia. In: Translational Psychiatry. 2017 ; Vol. 7, No. 6. pp. e1155.
@article{f87b6d7d52734c848b0d808db626ccf4,
title = "Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia",
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.",
author = "{Schizophrenia Working Group of the Psychiatric Genomics Consortium} and {Bipolar Disorders Working Group of the Psychiatric Genomics Consortium} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Witt, {S. H.} and F. Streit and M. Jungkunz and J. Frank and S. Awasthi and Reinbold, {C. S.} and J. Treutlein and F. Degenhardt and Forstner, {A. J.} and S. Heilmann-Heimbach and L. Dietl and Schwarze, {C. E.} and D. Schendel and J. Strohmaier and A. Abdellaoui and R. Adolfsson and Air, {T. M.} and H. Akil and M. Alda and N. Alliey-Rodriguez and Andreassen, {O. A.} and G. Babadjanova and Bass, {N. J.} and M. Bauer and Baune, {B. T.} and F. Bellivier and S. Bergen and A. Bethell and Biernacka, {Joanna M} and Blackwood, {D. H.R.} and Boks, {M. P.} and Boomsma, {D. I.} and B{\o}rglum, {A. D.} and M. Borrmann-Hassenbach and P. Brennan and M. Budde and Buttensch{\o}n, {H. N.} and Byrne, {E. M.} and P. Cervantes and Clarke, {T. K.} and N. Craddock and C. Cruceanu and D. Curtis and Czerski, {P. M.} and U. Dannlowski and T. Davis and {de Geus}, {E. J.C.} and {Di Florio}, A. and S. Djurovic and Frye, {Mark A}",
year = "2017",
month = "6",
day = "20",
doi = "10.1038/tp.2017.115",
language = "English (US)",
volume = "7",
pages = "e1155",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

AU - Bipolar Disorders Working Group of the Psychiatric Genomics Consortium

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Witt, S. H.

AU - Streit, F.

AU - Jungkunz, M.

AU - Frank, J.

AU - Awasthi, S.

AU - Reinbold, C. S.

AU - Treutlein, J.

AU - Degenhardt, F.

AU - Forstner, A. J.

AU - Heilmann-Heimbach, S.

AU - Dietl, L.

AU - Schwarze, C. E.

AU - Schendel, D.

AU - Strohmaier, J.

AU - Abdellaoui, A.

AU - Adolfsson, R.

AU - Air, T. M.

AU - Akil, H.

AU - Alda, M.

AU - Alliey-Rodriguez, N.

AU - Andreassen, O. A.

AU - Babadjanova, G.

AU - Bass, N. J.

AU - Bauer, M.

AU - Baune, B. T.

AU - Bellivier, F.

AU - Bergen, S.

AU - Bethell, A.

AU - Biernacka, Joanna M

AU - Blackwood, D. H.R.

AU - Boks, M. P.

AU - Boomsma, D. I.

AU - Børglum, A. D.

AU - Borrmann-Hassenbach, M.

AU - Brennan, P.

AU - Budde, M.

AU - Buttenschøn, H. N.

AU - Byrne, E. M.

AU - Cervantes, P.

AU - Clarke, T. K.

AU - Craddock, N.

AU - Cruceanu, C.

AU - Curtis, D.

AU - Czerski, P. M.

AU - Dannlowski, U.

AU - Davis, T.

AU - de Geus, E. J.C.

AU - Di Florio, A.

AU - Djurovic, S.

AU - Frye, Mark A

PY - 2017/6/20

Y1 - 2017/6/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85031737183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031737183&partnerID=8YFLogxK

U2 - 10.1038/tp.2017.115

DO - 10.1038/tp.2017.115

M3 - Article

C2 - 28632202

AN - SCOPUS:85031737183

VL - 7

SP - e1155

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

IS - 6

ER -