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Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes

Ruderfer, Douglas M., Ripke, Stephan, McQuillin, Andrew, Boocock, James, Stahl, Eli A., Pavlides, Jennifer M. Whitehead, Mullins, Niamh, Charney, Alexander W., Ori, Anil P.S., Loohuis, Loes M. 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Robert, Cohen, David, Cohen, Nadine, Coleman, Jonathan R.I., Collier, David A., Cormican, Paul, Coryell, William, Craddock, Nicholas, Craig, David W., Crespo-Facorro, Benedicto, Crowley, James J., Cruceanu, Cristiana, Curtis, David, Czerski, Piotr M., Dale, Anders M., Daly, Mark J., Dannlowski, Udo, Darvasi, Ariel, Davidson, Michael, Davis, Kenneth L., de Leeuw, Christiaan A., Degenhardt, Franziska, Del Favero, Jurgen, DeLisi, Lynn E., Deloukas, Panos, Demontis, Ditte, DePaulo, J. 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Scott, Su, Zhan, Subramaniam, Mythily, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Szelinger, Szabolcs, Tashakkori-Ghanbaria, Avazeh, Thirumalai, Srinivas, Thompson, Robert C., Thorgeirsson, Thorgeir E., Toncheva, Draga, Tooney, Paul A., Tosato, Sarah, Toulopoulou, Timothea, Trembath, Richard C., Treutlein, Jens, Trubetskoy, Vassily, Turecki, Gustavo, Vaaler, Arne E., Vedder, Helmut, Vieta, Eduard, Vincent, John, Visscher, Peter M., Viswanathan, Ananth C., Vukcevic, Damjan, Waddington, John, Waller, Matthew, Walsh, Dermot, Walshe, Muriel, Walters, James T.R., Wang, Dai, Wang, Qiang, Wang, Weiqing, Wang, Yunpeng, Watson, Stanley J., Webb, Bradley T., Weickert, Thomas W., Weinberger, Daniel R., Weisbrod, Matthias, Weiser, Mark, Werge, Thomas, Weston, Paul, Whittaker, Pamela, Widaa, Sara, Wiersma, Durk, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H.M., Wood, Nicholas W., Wormley, Brandon K., Wu, Jing Qin, Xi, Simon, Xu, Wei, Young, Allan H., Zai, Clement C., Zandi, Peter, Zhang, Peng, Zheng, Xuebin, Zimprich, Fritz, Zollner, Sebastian, Corvin, Aiden, Fanous, Ayman H., Cichon, Sven, Rietschel, Marcella, Gershon, Elliot S., Schulze, Thomas G., Cuellar-Barboza, Alfredo B., Forstner, Andreas J., Holmans, Peter A., Nurnberger, John I., Andreassen, Ole A., Lee, S. Hong, O'Donovan, Michael, Sullivan, Patrick F., Ophoff, Roel A., Wray, Naomi, Sklar, Pamela and Kendler, Kenneth S. 2018. Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes. Cell 173 (7) , pp. 1705-1715. 10.1016/j.cell.2018.05.046

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Abstract

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Healthcare Sciences
Medicine
Psychology
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Elsevier (Cell Press)
ISSN: 0092-8674
Date of First Compliant Deposit: 19 June 2018
Date of Acceptance: 21 May 2018
Last Modified: 17 Oct 2019 18:32
URI: http://orca-mwe.cf.ac.uk/id/eprint/112551

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