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

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

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Authors

  • 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
  • And 153 others
  • 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 Zoellner
  • Peng Zhang
  • David W. Craig
  • Szabocls Szelinger
  • Thomas B. Barrett
  • Rene 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 Guo 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. Noethen
  • 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
  • Keith Matthews
  • Allan H. Young
  • I. Nicol Ferrier
  • Richard Williamson
  • Kari Stefansson
  • Hreinn Stefansson
  • Porgeir Porgeirsson
  • Stacy Steinberg
  • Omar Gustafsson
  • Sarah E. Bergen
  • Vishwajit Nimgaonkar
  • Christina Hultman
  • Mikael Landen
  • Paul Lichtenstein
  • Patrick Sullivan
  • Martin Schalling
  • Urban Osby
  • Lena Backlund
  • Louise Frisen
  • Niklas Langstrom
  • Stephane Jamain
  • Marion Leboyer
  • Bruno Etain
  • Frank Bellivier
  • Hannes Petursson
  • Engilbert Sigurosson
  • Bertram Mueller-Mysok
  • Susanne Lucae
  • Markus Schwarz
  • Peter R. Schofield
  • Nick Martin
  • Grant W. Montgomery
  • Mark Lathrop
  • Hogni Oskarsson
  • Michael Bauer
  • Adam Wright
  • Philip B. Mitchell
  • Martin Hautzinger
  • Andreas Reif
  • John R. Kelsoe
  • Shaun M. Purcell
  • Psychiat GWAS Consortium Bipolar D

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Info

Original languageEnglish
Pages977-983
Number of pages7
JournalNature Genetics
Journal publication dateOct 2011
Volume43
Issue10
DOIs
StatePublished

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 x 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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