Universität zu Köln

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., Borglum, A. D., Borrmann-Hassenbach, M., Brennan, P., Budde, M., Buttenschon, 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., Jureus, A., Kahn, R. S., Kammerer-Ciernioch, J., Kirov, G., Kittel-Schneider, S., Kloiber, S., Knott, S. V., Kogevinas, M., Landen, 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., Muehleisen, T. W., Mueller-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., Tadic, A., Dahmen, N., Schott, B. H., Cichon, S., Noethen, 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. Transl. Psychiatr., 7. NEW YORK: NATURE PUBLISHING GROUP. 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 x 10(-7)) and PKP4 (P = 8.67 x 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 (r(g) = 0.28 [P = 2.99 x 10(-3)]), SCZ (r(g) = 0.34 [P = 4.37 x 10(-5)]) and MDD (r(g) = 0.57 [P = 1.04 x 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Witt, S. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Streit, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jungkunz, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frank, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Awasthi, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinbold, C. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Treutlein, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Degenhardt, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Forstner, A. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilmann-Heimbach, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dietl, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarze, C. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schendel, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Strohmaier, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abdellaoui, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Adolfsson, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Air, T. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Akil, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alda, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alliey-Rodriguez, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Andreassen, O. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Babadjanova, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bass, N. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baune, B. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bellivier, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergen, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bethell, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Biernacka, J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blackwood, D. H. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boks, M. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boomsma, D. I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Borglum, A. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Borrmann-Hassenbach, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brennan, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Budde, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buttenschon, H. N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Byrne, E. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cervantes, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Clarke, T-K UNSPECIFIED UNSPECIFIED UNSPECIFIED Craddock, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cruceanu, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Curtis, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Czerski, P. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dannlowski, U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Davis, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Geus, E. J. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Di Florio, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Djurovic, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Domenici, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Edenberg, H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Etain, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, S. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Forty, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fraser, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frye, M. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fullerton, J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gade, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gershon, E. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Giegling, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gordon, S. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gordon-Smith, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grabe, H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Green, E. K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Greenwood, T. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grigoroiu-Serbanescu, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Guzman-Parra, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hall, L. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamshere, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hauser, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hautzinger, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilbronner, U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herms, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hitturlingappa, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Holmans, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hottenga, J-J UNSPECIFIED UNSPECIFIED UNSPECIFIED Jamain, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jones, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jones, L. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jureus, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kahn, R. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kammerer-Ciernioch, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirov, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kittel-Schneider, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloiber, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knott, S. V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kogevinas, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Landen, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Leber, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Leboyer, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Q. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lissowska, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lucae, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, N. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mayoral-Cleries, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED McElroy, S. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED McIntosh, A. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED McKay, J. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED McQuillin, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Medland, S. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Middeldorp, C. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Milaneschi, Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mitchell, P. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Montgomery, G. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Morken, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mors, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Muehleisen, T. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller-Myhsok, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Myers, R. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nievergelt, C. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nurnberger, J. I. UNSPECIFIED UNSPECIFIED UNSPECIFIED O'Donovan, M. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Loohuis, L. M. O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ophoff, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oruc, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Owen, M. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paciga, S. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Penninx, B. W. J. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Perry, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfennig, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Potash, J. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Preisig, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reif, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rivas, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rouleau, G. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schofield, P. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulze, T. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scott, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sinnamon, G. C. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stahl, E. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Strauss, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Turecki, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Van der Auwera, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vedder, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vincent, J. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Willemsen, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Witt, C. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wray, N. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Xi, H. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tadic, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dahmen, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schott, B. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cichon, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Noethen, M. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ripke, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mobascher, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rujescu, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lieb, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Roepke, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmahl, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bohus, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rietschel, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-227572
DOI:	10.1038/tp.2017.115
Journal or Publication Title:	Transl. Psychiatr.
Volume:	7
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	2158-3188
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language METAANALYSIS; TRAITS; FAMILY; RISK; SET; PSYCHOPATHOLOGY; COMORBIDITY; PATTERNS; FEATURES; LOCI Multiple languages Psychiatry Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22757