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. HolmansDanyu 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

Research output: Contribution to journalArticle

895 Scopus citations

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 (US)
Pages (from-to)977-985
Number of pages9
JournalNature Genetics
Volume43
Issue number10
DOIs
StatePublished - Oct 2011

Fingerprint Dive into the research topics of 'Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4'. Together they form a unique fingerprint.

  • Cite this

    Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., Edenberg, H. J., Nurnberger, J. I., Rietschel, M., Blackwood, D., Corvin, A., Flickinger, M., Guan, W., Mattingsdal, M., McQuillin, A., Kwan, P., Wienker, T. F., Daly, M., Dudbridge, F., ... Purcell, S. M. (2011). Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature Genetics, 43(10), 977-985. https://doi.org/10.1038/ng.943