Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4

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  • A Corrigendum to this article was published on 29 August 2012


We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10−7). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.

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Figure 1: Results are shown as –log10P for genotyped and imputed SNPs.

Change history

  • 21 June 2012

    In the version of this article initially published, there were errors in the consortium membership list and the associated affiliations and in the acknowledgements and contributions sections. These errors and their corrections are detailed below by section. Consortium members: Janice M. Fullerton was omitted from the membership list and has now been added with affiliations 76 and 77. Phil H. Lee was listed incorrectly as Phil L. Hyoun. Fan Meng was listed incorrectly as Fan Guo Meng, and the associated affiliation has been changed from 51 to 54. Robert Thompson was assigned affiliation 50; the correct affiliation is 54. Marian Hamshere and Valentina Moskvina were assigned affiliation 26; the correct affiliation for both is 22. Richard Day was assigned affiliation 47; the correct affiliation is 46. Jun Li was assigned affiliation 24; the correct affiliation is 48. In addition to the affiliation originally listed for Sebastian Zöllner and Peng Zhang, both have now also been assigned affiliation 4. Howard Endenberg has now also been assigned affiliation 12, and Shaun Purcell has now also been assigned affiliation 1. Consortium affiliations: Affiliation 46 was originally given as the University of Dundee School of Medicine, Nethergate, Dundee, UK. The correct affiliation is the Division of Neuroscience, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK. Affiliation 47 was originally given as the School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Newcastle upon Tyne, UK. The correct affiliation is the Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA. This affiliation was also listed out of order and has now been changed to affiliation 48. Affiliation 76 was originally given as the Prince of Wales Medical Institute, Sydney, Australia. The correct affiliation is Neuroscience Research Australia, Sydney, Australia. Acknowledgments: The Stanley Foundation for Medical Research was listed as a source of funding. The correct name is the Stanley Medical Research Institute, and the Merck Genome Research Institute has also been added as a source of support. Contributions: In four instances, the contribution of Sven Cichon was indicated with the incorrect spelling S. Chichon instead of S. Cichon. Manuel A. Ferreira (M.A.F.) was incorrectly listed as a contributor to manuscript preparation. Manuel A. Ferreira (M.A.F.) was listed as a contributor to primary study data at the NIMH/Pritzke; the correct contributor was Matthew Flickinger (M.F.). In the section listing contributors to replication data, Neuroscience Research Australia was named incorrectly as the Prince of Wales Medical Institute, and Janice M. Fullerton (J.M.F.) has been added as a contributor at this site and at the University of New South Wales. The errors detailed above have been corrected in the HTML and PDF versions of the article. In addition, the subsections of the contributions section detailing the individuals contributing to primary study data and replication data were omitted from the original HTML version of the article, and this error has now been corrected.


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We would like to recognize the contribution of thousands of subjects without whom this work would not be possible. T. Lehner (National Institute of Mental Health (NIMH)) was instrumental in initiating and planning the overall project. D. Posthuma and the Dutch Genetic Cluster Computer provided invaluable computational resources. We also thank the PGC schizophrenia group for allowing us to perform the combined analyses of six loci before publication. This work was supported by many grants from the US National Institutes of Health (NIH) (MH078151, MH081804, MH059567 supplement, MH59553, MH080372 and 1U54RR025204). Other sources of support include: the Genetic Association Information Network (GAIN), the NIMH Intramural Research Program, the Tzedakah Foundation, the American Philosophical Society, the Stardust foundation, the National Library of Medicine, the Stanley Medical Research Institute, the Merck Genome Research Institute and the Wellcome Trust, the Pritzker Neuropsychiatric Disorders Research Fund L.L.C., GlaxoSmithKline, as well as grants for individual studies (see the Supplemental Note for a full list of Acknowledgements). The TOP Study was supported by grants from the Research Council of Norway (167153/V50, 163070/V50 and 175345/V50), the South-East Norway Health Authority (123-2004) and the EU (ENBREC). Additional acknowledgments can be found in the Supplementary Note.

Genotype data from this manuscript for the 10,257 samples can be obtained from the Center on Collaborative Genetic Studies of Mental Disorders in accordance with NIMH data release policies ( Genotype data from the WTCCC sample can be obtained from Genotype data from the BOMA-Bipolar Study can be obtained by contacting S. Cichon directly (

Author information

Manuscript preparation: P. Sklar. (chair), O.A.A., S. Cichon, N.C., H.J.E., J.R.K., J.I.N., S.M.P., M.R., S. Ripke, L.J.S. Analysis group: S.M.P. (chair), D.B., A.C., N.C., M.F., W.G., J.R.K., M. Mattingsdal, A. McQuillin, P.K., S. Ripke, L.J.S., P. Sklar, T.F.W. PGC central analysis group: S. Ripke (chair), M.D., F.D., P.A.H., D.L. Management group: J.R.K. (co-chair), P. Sklar. (co-chair), O.A.A., D.B., M. Burmeister, S. Cichon, N.C., T.A.G., M.L.H., S.M.P., P. Muglia, J.I.N., L.J.S., E.N.S., P.P.Z.

Primary study data was contributed from the following investigators: BiGS (Bipolar Genome Study) –University of California San Diego: J.R.K., T.A.G., C.M.N., R.M., P.D.S.; Scripps Translational Science Institute: N.J.S., E.N.S., C.S.B.; Indiana University: J.I.N., H.J.E., T.F., D.L.K.; University of Chicago: E.S.G., C.L., J.A.B.; Rush University Medical Center: W.A.S.; Howard University: W.B.L., E.A.N., M. Hipolito; University of Iowa: W.C.; Washington University: J.R.; University of California San Francisco: W. Byerley; National Institute of Mental Health: F.J.M., T.G.S.; University of Pennsylvania: W. Berrettini, F.W.L.; Johns Hopkins Hospital: J.B.P., P.P.Z., P.B. Mahon; University of Michigan: M.G.M., S.Z., P.Z.; The Translational Genomics Research Institute: D.W.C., S. Szelinger; Portland Veterans Affairs Medical Center: T.B.B.; Central Institute of Mental Health, Mannheim: R.B., S.M., M.R., T.G.S., J. Strohmaier, S.H.W.; GlaxoSmithKline, Institute of Psychiatry, Centre for Addiction & Mental Health, University of Dundee: F.T., P. Muglia, A.F., P. McGuffin, J. Strauss, W.X., J.L.K., J.B.V., K. Matthews, R.D.; Massachusetts General Hospital: M.A.F., C.O.'D., R.P., S.M.P., S. Raychaudhuri, P.L.H., D.R., P. Sklar, J.W.S.; NIMH/Pritzker: L.J.S., M.F., M. Burmeister, J. Li, W.G., P.K., D.A., R.C.T., F.G.M., A.F.S., W.E.B., J.D.B., E.G.J., S.J.W., R.M.M., H.A., M. Boehnke; Stanley Center Broad Institute: K.C., J.M., E. Scolnick; TOP Study Group: O.A.A., S.D., M. Mattingsdal, I.M., G.M.; Trinity College Dublin: A.C., M.G., D.M., E.Q.; University of Bonn: S. Cichon, T.W.M., F.A.D., M. Mattheisen, J. Schumacher, W.M., M. Steffens, T.F.W., P.P., M.M.N.; University College London: A.A., N.B., H.G., R.K., J. Lawrence, A. McQuillin; University of Edinburgh: D.B., K. McGhee, A. McIntosh, A.W.M., W.J.M., B.S.P.; Wellcome Trust Case Control Consortium Bipolar Disorder GroupAberdeen: G.B., D.St.C.; Birmingham: S. Caesar, K.G.-S., L.J.; Cardiff: C.F., E.K.G., D.G., M.L.H., P.A.H., I.R.J., G.K., V.M., I.N., M.C.O., M.J.O., N.C.; London: D.A.C., A.E., A.F., R.W., P. McGuffin; Newcastle: A.H.Y., I.N.F. Replication data contributed by the following investigators: Central Institute of Mental Health, Mannheim: R.B., S.M., M.R., T.G.S., J. Strohmaier, S.H.W.; deCODE genetics: H.S., Þ.Þ., S. Steinberg, Ó.G., K.S.; FaST: S.E.B., K.C., J.M., V.N., S.M.P., P. Sklar, J.W.S.; ICCBD: C.H., M. Landén, P.L., P. Sullivan, M. Schalling, U.O., L.B., L.F., S.E.B., S.M.P., K.C., J.M., N.L., P. Sklar; INSERM U955: S.J., M. Leboyer, B.E., F.B.; Landspitali University: H.P., E. Sigurđsson; Max Planck Institute of Psychiatry, Munich: B.M.-M., S.L.; Psychiatric Center Nordbaden: M. Schwarz; Neuroscience Research Australia and University of New South Wales: P.R.S. and J.M.F.; Queensland Institute of Medical Research: N.M., G.W.M.; Centre National de Génotypage: M. Lathrop; Therapeia University Hospital, Reykjavík: H.Ó.; University of Bonn: S. Cichon, T.W.M., F.A.D., M. Mattheisen, J. Schumacher, W.M., M. Steffens, T.F.W., P.P., M.M.N.; University of Dresden: M. Bauer; University of New South Wales and Black Dog Institute: A.W., P.B. Mitchell; University of Tübingen: M. Hautzinger; University of Würzburg: A.R.

Correspondence to Pamela Sklar.

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