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Genome-wide Association Study Identifies 30 Loci Associated with Bipolar Disorder

Stahl, E.A., Breen, G., Forstner, A.J., McQuillin, A., Ripke, S., Trubetskoy, V., Mattheisen, M., Wang, Y., Coleman, J.R.I., Gaspar, H.A., de Leeuw, C.A., Steinberg, S., Whitehead Pavlides, J.M., Trzaskowski, M., Byrne, E.M., Pers, T.H., Holmans, P.A., Richards, A.L., Abbott, L., Agerbo, E., Akil, H., Albani, D., Alliey-Rodriguez, N., Als, T.D., Anjorin, A., Antilla, V., Awasthi, S., Badner, J.A., Bækvad-Hansen, M., Barchas, J.D., Bass, N., Bauer, M., Belliveau, R., Bergen, S.E., Pedersen, C.B., Bøen, E., Boks, M., Boocock, J., Budde, M., Bunney, W., Burmeister, M., Bybjerg-Grauholm, J., Byerley, W., Casas, M., Cerrato, F., Cervantes, P., Chambert, K., Charney, A.W., Chen, D., Churchhouse, C., Clarke, T.K., Coryell, W., Craig, D.W., Cruceanu, C., Curtis, D., Czerski, P.M., Dale, A.M., de Jong, S., Degenhardt, F., Del-Favero, J., DePaulo, J.R., Djurovic, S., Dobbyn, A.L., Dumont, A., Elvsåshagen, T., Escott-Price, V., Fan, C.C., Fischer, S.B., Flickinger, M., Foroud, T.M., Forty, L., Frank, J., Fraser, C., Freimer, N.B., Frisén, L., Gade, K., Gage, D., Garnham, J., Giambartolomei, C., Pedersen, M.G., Goldstein, J., Gordon, S.D., Gordon-Smith, Katherine, Green, E.K., Green, M.J., Greenwood, T.A., Grove, J., Guan, W., Guzman-Parra, J., Hamshere, M.L., Hautzinger, M., Heilbronner, U., Herms, S., Hipolito, M., Hoffmann, P., Holland, D., Huckins, L., Jamain, S., Johnson, J.S., Juréus, A., Kandaswamy, R., Karlsson, R., Kennedy, J.L., Kittel-Schneider, S., Knowles, J.A., Kogevinas, M., Koller, A.C., Kupka, R., Lavebratt, C., Lawrence, J., Lawson, W.B., Leber, M., Lee, P.H., Levy, S.E., Li, J.Z., Liu, C., Lucae, S., Maaser, A., MacIntyre, D.J., Mahon, P.B., Maier, W., Martinsson, L., McCarroll, S., McGuffin, P., McInnis, M.G., McKay, J.D., Medeiros, H., Medland, S.E., Meng, F., Milani, L., Montgomery, G.W., Morris, D.W., Mühleisen, T.W., Mullins, N., Nguyen, H., Nievergelt, C.M., Adolfsson, A.N., Nwulia, E.A., O’Donovan, C., Loohuis, L.M.O., Ori, A.P.S., Oruc, L., Ösby, U., Perlis, R.H., Perry, Amy, Pfennig, A., Potash, J.B., Purcell, S.M., Regeer, E.J., Reif, A., Reinbold, C.S., Rice, J.P., Rivas, F., Rivera, M., Roussos, P., Ruderfer, D.M., Ryu, E., Sánchez-Mora, C., Schatzberg, A.F., Scheftner, W.A., Schork, N.J., Shannon Weickert, C., Shehktman, T., Shilling, P.D., Sigurdsson, E., Slaney, C., Smeland, O.B., Sobell, J.L., Søholm Hansen, C., Spijker, A.T., St Clair, D., Steffens, M., Strauss, J.S., Streit, F., Strohmaier, J., Szelinger, S., Thompson, R.C., Thorgeirsson, T.E., Treutlein, J., Vedder, H., Wang, W., Watson, S.J., Weickert, T.W., Witt, S.H., Xi, S., Xu, W., Young, A.H., Zandi, P., Zhang, P., Zöllner, S., Adolfsson, R., Agartz, I., Alda, M., Backlund, L., Baune, B.T., Bellivier, F., Berrettini, W.H., Biernacka, J.M., Blackwood, D.H.R., Boehnke, M., Børglum, A.D., Corvin, A., Craddock, N., Daly, M.J., Dannlowski, U., Esko, T., Etain, B., Frye, M., Fullerton, J.M., Gershon, E.S., Gill, M., Goes, F., Grigoroiu-Serbanescu, M., Hauser, J., Hougaard, D.M., Hultman, C.M., Jones, I., Jones, Lisa, Kahn, R.S., Kirov, G., Landén, M., Leboyer, M., Lewis, C.M., Li, Q.S., Lissowska, J., Martin, N.G., Mayoral, F., McElroy, S.L., McIntosh, A.M., McMahon, F.J., Melle, I., Metspalu, A., Mitchell, P.B., Morken, G., Mors, O., Mortensen, P.B., Müller-Myhsok, B., Myers, R.M., Neale, B.M., Nimgaonkar, V., Nordentoft, M., Nöthen, M.M., O’Donovan, M.C., Oedegaard, K.J., Owen, M.J., Paciga, S.A., Pato, C., Pato, M.T., Posthuma, D., Ramos-Quiroga, J.A., Ribasés, M., Rietschel, M., Rouleau, G.A., Schalling, M., Schofield, P.R., Schulze, T.G., Serretti, A., Smoller, J.W., Stefansson, H., Stefansson, K., Stordal, E., Sullivan, P.F., Turecki, G., Vaaler, A.E., Vieta, E., Vincent, J.B., Werge, T., Nurnberger, J.I., Wray, N.R., Di Florio, A., Edenberg, H.J., Cichon, S., Ophoff, R.A., Scott, L.J., Andreassen, O.A., Kelsoe, J. and Sklar, P. (2019) Genome-wide Association Study Identifies 30 Loci Associated with Bipolar Disorder. Nature Genetics, 51 (5). pp. 793-803. ISSN Online: 1546-1718

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Abstract

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10−4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10−8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

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Uncontrolled Keywords: genetic association study, psychiatric disorders, genetic research, genomics, medical genetics, bipolar disorder
Divisions: Divisions (2019 and before) > Academic Departments > Institute of Health and Society
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Depositing User: Katherine Gordon-Smith
Date Deposited: 08 May 2019 14:11
Last Modified: 09 Oct 2019 08:34
URI: https://eprints.worc.ac.uk/id/eprint/7954

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