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

Witt, S.H.; Streit, F.; Jungkunz, M.; Frank, J.; Awasthi, S.; Reinbold, C.S.; Treutlein, J.; Degenhardt, F.; Forstner, A.J.; Heilmann-Heimbach, S.; Dietl, L.; Schwarze, C.E.; Schendel, D.; Strohmaier, J.; Abdellaoui, A.; Adolfsson, R.; Air, T.M.; Akil, H.; Alda, M.; Alliey-Rodriguez, N.; Andreassen, O.A.; Babadjanova, G.; Bass, N.J.; Bauer, M.; Baune, B.T.; Bellivier, F.; Bergen, S.; Bethell, A.; Biernacka, J.M.; Blackwood, DHR; Boks, M.P.; Boomsma, D.I.; Børglum, A.D.; Borrmann-Hassenbach, M.; Brennan, P.; Budde, M.; Buttenschøn, H.N.; Byrne, E.M.; Cervantes, P.; Clarke, T.K.; Craddock, N.; Cruceanu, C.; Curtis, D.; Czerski, P.M.; Dannlowski, U.; Davis, T.; de Geus, EJC; Di Florio, A.; Djurovic, S.; Domenici, E.; Edenberg, H.J.; Etain, B.; Fischer, S.B.; Forty, L.; Fraser, C.; Frye, M.A.; Fullerton, J.M.; Gade, K.; Gershon, E.S.; Giegling, I.; Gordon, S.D.; Gordon-Smith, K.; Grabe, H.J.; Green, E.K.; Greenwood, T.A.; Grigoroiu-Serbanescu, M.; Guzman-Parra, J.; Hall, L.S.; Hamshere, M.; Hauser, J.; Hautzinger, M.; Heilbronner, U.; Herms, S.; Hitturlingappa, S.; Hoffmann, P.; Holmans, P.; Hottenga, J.J.; Jamain, S.; Jones, I.; Jones, L.A.; Juréus, A.; Kahn, R.S.; Kammerer-Ciernioch, J.; Kirov, G.; Kittel-Schneider, S.; Kloiber, S.; Knott, S.V.; Kogevinas, M.; Landén, M.; Leber, M.; Leboyer, M.; Li, Q.S.; Lissowska, J.; Lucae, S.; Martin, N.G.; Mayoral-Cleries, F.; McElroy, S.L.; McIntosh, A.M.; McKay, J.D.; McQuillin, A.; Medland, S.E.; Middeldorp, C.M.; Milaneschi, Y.; Mitchell, P.B.; Montgomery, G.W.; Morken, G.; Mors, O.; Mühleisen, T.W.; Müller-Myhsok, B.; Myers, R.M.; Nievergelt, C.M.; Nurnberger, J.I.; O'Donovan, M.C.; Loohuis, LMO; Ophoff, R.; Oruc, L.; Owen, M.J.; Paciga, S.A.; Penninx, BWJH; Perry, A.; Pfennig, A.; Potash, J.B.; Preisig, M.; Reif, A.; Rivas, F.; Rouleau, G.A.; Schofield, P.R.; Schulze, T.G.; Schwarz, M.; Scott, L.; Sinnamon, GCB; Stahl, E.A.; Strauss, J.; Turecki, G.; Van der Auwera, S.; Vedder, H.; Vincent, J.B.; Willemsen, G.; Witt, C.C.; Wray, N.R.; Xi, H.S.; Tadic, A.; Dahmen, N.; Schott, B.H.; Cichon, S.; Nöthen, M.M.; Ripke, S.; Mobascher, A.; Rujescu, D.; Lieb, K.; Roepke, S.; Schmahl, C.; Bohus, M.; Rietschel, M.

doi:10.1038/tp.2017.115

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

Details

Download: 28632202_BIB_BD432F7112DC.pdf (780.82 [Ko])
State: Public
Version: Final published version

Serval ID

serval:BIB_BD432F7112DC

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Translational psychiatry

Author(s)

Witt S.H., Streit F., Jungkunz M., Frank J., Awasthi S., Reinbold C.S., Treutlein J., Degenhardt F., Forstner A.J., Heilmann-Heimbach S., Dietl L., Schwarze C.E., Schendel D., Strohmaier J., Abdellaoui A., Adolfsson R., Air T.M., Akil H., Alda M., Alliey-Rodriguez N., Andreassen O.A., Babadjanova G., Bass N.J., Bauer M., Baune B.T., Bellivier F., Bergen S., Bethell A., Biernacka J.M., Blackwood DHR, Boks M.P., Boomsma D.I., Børglum A.D., Borrmann-Hassenbach M., Brennan P., Budde M., Buttenschøn H.N., Byrne E.M., Cervantes P., Clarke T.K., Craddock N., Cruceanu C., Curtis D., Czerski P.M., Dannlowski U., Davis T., de Geus EJC, Di Florio A., Djurovic S., Domenici E., Edenberg H.J., Etain B., Fischer S.B., Forty L., Fraser C., Frye M.A., Fullerton J.M., Gade K., Gershon E.S., Giegling I., Gordon S.D., Gordon-Smith K., Grabe H.J., Green E.K., Greenwood T.A., Grigoroiu-Serbanescu M., Guzman-Parra J., Hall L.S., Hamshere M., Hauser J., Hautzinger M., Heilbronner U., Herms S., Hitturlingappa S., Hoffmann P., Holmans P., Hottenga J.J., Jamain S., Jones I., Jones L.A., Juréus A., Kahn R.S., Kammerer-Ciernioch J., Kirov G., Kittel-Schneider S., Kloiber S., Knott S.V., Kogevinas M., Landén M., Leber M., Leboyer M., Li Q.S., Lissowska J., Lucae S., Martin N.G., Mayoral-Cleries F., McElroy S.L., McIntosh A.M., McKay J.D., McQuillin A., Medland S.E., Middeldorp C.M., Milaneschi Y., Mitchell P.B., Montgomery G.W., Morken G., Mors O., Mühleisen T.W., Müller-Myhsok B., Myers R.M., Nievergelt C.M., Nurnberger J.I., O'Donovan M.C., Loohuis LMO, Ophoff R., Oruc L., Owen M.J., Paciga S.A., Penninx BWJH, Perry A., Pfennig A., Potash J.B., Preisig M., Reif A., Rivas F., Rouleau G.A., Schofield P.R., Schulze T.G., Schwarz M., Scott L., Sinnamon GCB, Stahl E.A., Strauss J., Turecki G., Van der Auwera S., Vedder H., Vincent J.B., Willemsen G., Witt C.C., Wray N.R., Xi H.S., Tadic A., Dahmen N., Schott B.H., Cichon S., Nöthen M.M., Ripke S., Mobascher A., Rujescu D., Lieb K., Roepke S., Schmahl C., Bohus M., Rietschel M.

Working group(s)

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

ISSN

2158-3188 (Electronic)

ISSN-L

2158-3188

Publication state

Published

Issued date

20/06/2017

Peer-reviewed

Oui

Volume

Number

Pages

e1155

Language

english

Notes

Publication types: Journal Article
Publication Status: epublish

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 javax.xml.bind.JAXBElement@2dfb8703 ) and PKP4 (P=8.67 × 10 javax.xml.bind.JAXBElement@2a06c633 ); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P javax.xml.bind.JAXBElement@436b9be1 =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 (r javax.xml.bind.JAXBElement@683a14e0 =0.28 [P=2.99 × 10 javax.xml.bind.JAXBElement@1988457b ]), SCZ (r javax.xml.bind.JAXBElement@5232f27 =0.34 [P=4.37 × 10 javax.xml.bind.JAXBElement@1a0818f1 ]) and MDD (r javax.xml.bind.JAXBElement@222d9244 =0.57 [P=1.04 × 10 javax.xml.bind.JAXBElement@79d5b8e7 ]). 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.

Keywords

Adolescent, Adult, Aged, Bipolar Disorder/genetics, Borderline Personality Disorder/genetics, Case-Control Studies, Depressive Disorder, Major/genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Multifactorial Inheritance, Schizophrenia/genetics, Young Adult

URN

urn:nbn:ch:serval-BIB_BD432F7112DC1

OAI-PMH

oai:serval.unil.ch:BIB_BD432F7112DC

DOI

10.1038/tp.2017.115

Pubmed

28632202

Web of science

000403846500002

Open Access

Yes