Abstract
To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 × 10−9) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 × 10−8, rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.
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Acknowledgements
Study supported by US National Institute of Mental Health (MH062137, MH067288, P.S.; MH063445, J.W.S.; MH63420, V.L.N.; N01MH80001, G.S.S., M.E.T. and M.S. Bauer), NARSAD (R.H.P., S.P., J.F., P.S.); Johnson & Johnson Pharmaceutical Research & Development, Sylvan C. Herman Foundation, Stanley Medical Research Institute, Dauten Family, Merck Genome Research Institute (E.M.S.); and National Health Medical Research Council (MRC), Australia (M.A.R.F.). Broad Institute Center for Genotyping and Analysis supported by U54 RR020278, National Center for Research Resources. UCL sample collection supported by MDF–The Bipolar Organization, Neuroscience Research Charitable Trust, central London NHS Blood Transfusion Service, Priory Hospitals and UK MRC (G9623693N, G0500791). Dublin sample collection supported by the Health Research Board and Science Foundation Ireland; controls supplied by J. McPartlin, Trinity College Biobank. Edinburgh cohort collection supported by the Wellcome Trust, London, Chief Scientist Office of the Scottish Executive and MRC, London. WTCCC genotype analyses were funded by the Wellcome Trust and undertaken within the context of the WTCCC. WTCCC members are listed in Supplementary Note.
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Writing group: M.A.R.F., P.S., N.C., S.M.P. Analytic group: S.M.P., M.A.R.F., Y.A.M., D.M.R., J. Fan, M.J.D., P.A.H., M.C.O. N.C., P.S. Project management: P.S., E.M.S., A.P.C., D.H.B., H.M.G., M.C.O., N.C. Clinical characterization for STEP-BD: J.W.S., V.L.N., R.H.P., M.E.T., G.S.S. Clinical characterization for Trinity College Dublin: D.W.M., M.G., A.P.C. Clinical characterization for University of Edinburgh: W.J.M., K.A.M., D.J.M., A.W.M., M.V.B., D.H.B. Clinical characterization for University College London: A. McQuillin, N.J.B., M.R., J.L., A.C.P.P., R.K, A.A., D.C., H.M.G. Clinical characterization, phenotype assessment and sample management and curation for WTCCC: G.B., D.S. (Aberdeen); S.C., K.G.-S. L.J. (Birmingham); 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. (Cardiff); D.A.C., A.E., A.F., R.W., P.M. (London); A.H.Y., I.N.F. (Newcastle). DNA sample QC and genotyping for ED-DUB-STEP2: K.C., J.S., J. Fan, J. Franklin, K.G.A., S.B.G., B.B., M.D.
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A full list of members is provided in the Supplementary Note.
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Supplementary Methods, Supplementary Figures 1–5, Supplementary Tables 1–10, Supplementary Note (PDF 8946 kb)
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Ferreira, M., O'Donovan, M., Meng, Y. et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 40, 1056–1058 (2008). https://doi.org/10.1038/ng.209
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DOI: https://doi.org/10.1038/ng.209
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