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, D. H. R., 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, E. J. C., 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, L. M. O., Ophoff, R., Oruc, L., Owen, M. J., Paciga, S. A., Penninx, B. W. J. H., 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, G. C. B., 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., 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, 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. and Rietschel, M. (2017) Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia. Translational Psychiatry, 7 6: e1155.1-e1155.9. doi:10.1038/tp.2017.115


Author 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, D. H. R.
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, E. J. C.
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, L. M. O.
Ophoff, R.
Oruc, L.
Owen, M. J.
Paciga, S. A.
Penninx, B. W. J. H.
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, G. C. B.
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.
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
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.
Title Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia
Journal name Translational Psychiatry   Check publisher's open access policy
ISSN 2158-3188
Publication date 2017-06-20
Sub-type Article (original research)
DOI 10.1038/tp.2017.115
Open Access Status DOI
Volume 7
Issue 6
Start page e1155.1
End page e1155.9
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Fri, 23 Jun 2017, 01:01:49 EST