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

  • Pamela Sklar
  • , Stephan Ripke
  • , Laura J. Scott
  • , Ole A. Andreassen
  • , Sven Cichon
  • , Nick Craddock
  • , Howard J. Edenberg
  • , John I. Nurnberger
  • , Marcella Rietschel
  • , Douglas Blackwood
  • , Aiden Corvin
  • , Matthew Flickinger
  • , Weihua Guan
  • , Morten Mattingsdal
  • , Andrew McQuillin
  • , Phoenix Kwan
  • , Thomas F. Wienker
  • , Mark Daly
  • , Frank Dudbridge
  • , Peter A. Holmans
  • Danyu Lin, Margit Burmeister, Tiffany A. Greenwood, Marian L. Hamshere, Pierandrea Muglia, Erin N. Smith, Peter P. Zandi, Caroline M. Nievergelt, Rebecca McKinney, Paul D. Shilling, Nicholas J. Schork, Cinnamon S. Bloss, Tatiana Foroud, Daniel L. Koller, Elliot S. Gershon, Chunyu Liu, Judith A. Badner, William A. Scheftner, William B. Lawson, Evaristus A. Nwulia, Maria Hipolito, William Coryell, John Rice, William Byerley, Francis J. McMahon, Thomas G. Schulze, Wade Berrettini, Falk W. Lohoff, James B. Potash, Pamela B. Mahon, Melvin G. McInnis, Sebastian Zöllner, Peng Zhang, David W. Craig, Szabocls Szelinger, Thomas B. Barrett, René Breuer, Sandra Meier, Jana Strohmaier, Stephanie H. Witt, Federica Tozzi, Anne Farmer, Peter McGuffin, John Strauss, Wei Xu, James L. Kennedy, John B. Vincent, Keith Matthews, Richard Day, Manuel A. Ferreira, Colm O'Dushlaine, Roy Perlis, Soumya Raychaudhuri, Douglas Ruderfer, Phil H. Lee, Jordan W. Smoller, Jun Li, Devin Absher, William E. Bunney, Jack D. Barchas, Alan F. Schatzberg, Edward G. Jones, Fan Meng, Robert C. Thompson, Stanley J. Watson, Richard M. Myers, Huda Akil, Michael Boehnke, Kim Chambert, Jennifer Moran, Ed Scolnick, Srdjan Djurovic, Ingrid Melle, Gunnar Morken, Michael Gill, Derek Morris, Emma Quinn, Thomas W. Mühleisen, Franziska A. Degenhardt, Manuel Mattheisen, Johannes Schumacher, Wolfgang Maier, Michael Steffens, Peter Propping, Markus M. Nöthen, Adebayo Anjorin, Nick Bass, Hugh Gurling, Radhika Kandaswamy, Jacob Lawrence, Kevin McGhee, Andrew McIntosh, Alan W. McLean, Walter J. Muir, Benjamin S. Pickard, Gerome Breen, David St. Clair, Sian Caesar, Katherine Gordon-Smith, Lisa Jones, Christine Fraser, Elaine K. Green, Detelina Grozeva, Ian R. Jones, George Kirov, Valentina Moskvina, Ivan Nikolov, Michael C. O'Donovan, Michael J. Owen, David A. Collier, Amanda Elkin, Richard Williamson, Allan H. Young, I. Nicol Ferrier, Kari Stefansson, Hreinn Stefansson, Porgeir Porgeirsson, Stacy Steinberg, Ómar Gustafsson, Sarah E. Bergen, Vishwajit Nimgaonkar, Christina Hultman, Mikael Landén, Paul Lichtenstein, Patrick Sullivan, Martin Schalling, Urban Osby, Lena Backlund, Louise Frisén, Niklas Langstrom, Stéphane Jamain, Marion Leboyer, Bruno Etain, Frank Bellivier, Hannes Petursson, Engilbert Sigurdsson, Bertram Müller-Mysok, Susanne Lucae, Markus Schwarz, Janice M. Fullerton, Peter R. Schofield, Nick Martin, Grant W. Montgomery, Mark Lathrop, Högni Óskarsson, Michael Bauer, Adam Wright, Philip B. Mitchell, Martin Hautzinger, Andreas Reif, John R. Kelsoe, Shaun M. Purcell
  • Icahn School of Medicine at Mount Sinai
  • Massachusetts General Hospital
  • Broad Institute
  • University of Michigan, Ann Arbor
  • University of Oslo
  • Oslo University Hospital
  • University of Bonn
  • ICS-6/Structural Biochemistry
  • Cardiff University
  • Indiana University School of Medicine
  • Heidelberg University
  • University of Edinburgh
  • Trinity College Dublin
  • Sorlandet Hospital HF
  • University College London
  • London School of Hygiene and Tropical Medicine
  • Cardiff University School of Medicine
  • University of North Carolina at Chapel Hill
  • University of Michigan Medical School
  • University of California San Diego
  • GlaxoSmithKline SpA
  • Scripps Translational Science Institute
  • Ciccarone Center for the Prevention of Heart Disease
  • University of Chicago
  • Rush University Medical Center
  • Howard University College of Medicine
  • University of Iowa Carver College of Medicine
  • Washington University School of Medicine in St. Louis
  • University of California San Francisco
  • National Institute of Mental Health Intramural Research Program
  • Georg-August-Universität Göttingen
  • University of Pennsylvania
  • University of Michigan Medical Center
  • Translational Genomics Research Institute
  • Oregon Health Sciences University and Veterans Affairs Medical Center
  • King's College London
  • Centre for Addiction and Mental Health
  • Princess Margaret Hospital
  • University of Dundee School of Medicine
  • QIMR Berghofer Medical Research Institute
  • HudsonAlpha Institute for Biotechnology
  • University of California
  • Joan and Sanford I. Weill Department of Medicine
  • Stanford University School of Medicine
  • University of California
  • University of Michigan
  • Trondheim University Hospital
  • Norwegian University of Science and Technology (NTNU)
  • University of Aberdeen School of Medicine, Medical Sciences and Nutrition
  • University of Birmingham
  • University of British Columbia
  • deCODE genetics
  • University of Pittsburgh
  • Karolinska Institutet
  • University of Gothenburg
  • University of North Carolina
  • “Translationnal Psychiatry”
  • Université Paris-Est Créteil Val de Marne
  • University Paris East
  • ENBREC group
  • Landspitali - The National University Hospital of Iceland
  • Max Planck Institute of Psychiatry
  • Psychiatric Center Nordbaden
  • Neuroscience Research Australia
  • University of New South Wales
  • Commissariat À l'Energie Atomique
  • Therapeia
  • University Hospital Carl Gustav Carus
  • University of New South Wales Faculty of Medicine, School of Psychiatry
  • University of Tübingen
  • University of Wuerzburg
  • VA San Diego Healthcare System

Research output: Contribution to a Journal (Peer & Non Peer)Articlepeer-review

1125 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)977-985
Number of pages9
JournalNature Genetics
Volume43
Issue number10
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

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