Brief Communication abstract

Nature Genetics 40, 1056 - 1058 (2008)
Published online: 17 August 2008 | doi:10.1038/ng.209

Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder

Manuel A R Ferreira1,2,3,4,5,6, Michael C O'Donovan7, Yan A Meng1,2,3,4,5, Ian R Jones7, Douglas M Ruderfer1,3,4,5, Lisa Jones8, Jinbo Fan1,3,4,5, George Kirov7, Roy H Perlis1,2,3,4,5, Elaine K Green7, Jordan W Smoller1,2,3,4,5, Detelina Grozeva7, Jennifer Stone1,2,3,4,5, Ivan Nikolov7,9, Kimberly Chambert4,5, Marian L Hamshere7,9, Vishwajit L Nimgaonkar10, Valentina Moskvina7,9, Michael E Thase11,12, Sian Caesar8, Gary S Sachs1,2, Jennifer Franklin5, Katherine Gordon-Smith7,8, Kristin G Ardlie5, Stacey B Gabriel5, Christine Fraser7, Brendan Blumenstiel5, Matthew Defelice5, Gerome Breen13,14, Michael Gill15, Derek W Morris15, Amanda Elkin14, Walter J Muir16, Kevin A McGhee16, Richard Williamson14, Donald J MacIntyre16, Alan W MacLean16, David St Clair13, Michelle Robinson17, Margaret Van Beck16, Ana C P Pereira17, Radhika Kandaswamy17, Andrew McQuillin17, David A Collier14, Nicholas J Bass17, Allan H Young18,19, Jacob Lawrence17, I Nicol Ferrier18, Adebayo Anjorin17, Anne Farmer14, David Curtis17, Edward M Scolnick4,5,20, Peter McGuffin14, Mark J Daly5,21,22,23, Aiden P Corvin15, Peter A Holmans7,9, Douglas H Blackwood16, Wellcome Trust Case Control Consortium24, Hugh M Gurling17, Michael J Owen7, Shaun M Purcell1,2,3,4,5,25, Pamela Sklar1,2,3,4,5,20,25 & Nick Craddock7,25

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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 times 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 times 10-8, rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder.

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  1. Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  2. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115, USA.
  3. Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  4. Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  5. Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  6. Genetic Epidemiology, Queensland Institute of Medical Research, QLD 4029, Australia.
  7. Department of Psychological Medicine, Henry Wellcome Building, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
  8. Department of Psychiatry, Division of Neuroscience, Birmingham University, Birmingham B15 2QZ, UK.
  9. Biostatistics and Bioinformatics Unit, Henry Wellcome Building, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
  10. University of Pittsburgh, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania 15213, USA.
  11. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
  12. University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
  13. University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.
  14. SGDP, The Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.
  15. Trinity Centre for Health Sciences, St James's Hospital, Trinity College Dublin, Dublin 8, Republic of Ireland.
  16. Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK.
  17. Molecular Psychiatry Laboratory, Department of Mental Health Sciences, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, London W1T 4JF, UK.
  18. School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK.
  19. UBC Institute of Mental Health, 2255 Wesbrook Mall, Detwiller Pavilion Vancouver, British Columbia, Canada V6T 2A1.
  20. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
  21. Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
  22. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  23. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  24. A full list of members is provided in the Supplementary Note online.
  25. These authors contributed equally to this work.

Correspondence to: Pamela Sklar1,2,3,4,5,20,25 e-mail: sklar@chgr.mgh.harvard.edu

Correspondence to: Nick Craddock7,25 e-mail: craddockn@Cardiff.ac.uk



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