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

Pamela Sklar 1, 2, * Stephan Ripke 2, 3 Laura Scott 4 Ole Andreassen 5, 6 Sven Cichon 7, 8, 9 Nick Craddock 10 Howard Edenberg 11 John Nurnberger 12, 13 Marcella Rietschel 14 Douglas Blackwood 15, 16 Aiden Corvin 17 Matthew Flickinger 4 Weihua Guan 4 Morten Mattingsdal 5, 18 Andrew Mcquillin 19 Phoenix Kwan 4 Thomas Wienker 20 Mark Daly 2, 3 Frank Dudbridge 21 Peter Holmans 10, 22 Danyu Lin 23 Margit Burmeister 24 Tiffany Greenwood 25 Marian Hamshere 10, 26 Pierandrea Muglia 26 Erin Smith 27 Peter Zandi 28 Caroline Nievergelt 25 Rebecca Mckinney 25 Paul Shilling 25 Nicholas Schork 29 Cinnamon Bloss 27 Tatiana Foroud 12 Daniel Koller 12 Elliot Gershon 30 Chunyu Liu 30 Judith Badner 30 William Scheftner 31 William Lawson 32 Evaristus Nwulia 32 Maria Hipolito 32 William Coryell 33 John Rice 34 William Byerley 35 Francis Mcmahon 36 Thomas Schulze 14, 36, 37 Wade Berrettini 38 Falk Lohoff 38 James Potash 28 Pamela Mahon 28 Melvin Mcinnis 39 Sebastian Zöllner 39 Peng Zhang 39 David Craig 40 Szabocls Szelinger 40 Thomas Barrett 41 René Breuer 14 Sandra Meier 14 Jana Strohmaier 14 Stephanie Witt 14 Federica Tozzi 26 Anne Farmer 42 Peter Mcguffin 42 John Strauss 43 Wei Xu 44 James Kennedy 45 John Vincent 43 Keith Matthews 46 Richard Day 47 Manuel Ferreira 2, 3, 48 Colm O'Dushlaine 2, 3 Roy Perlis 2, 3 Soumya Raychaudhuri 2, 3 Douglas Ruderfer 2, 3 Phil Hyoun 2 Jordan Smoller 3, 2 Jun Li 24 Devin Absher 49 Robert Thompson 50 Fan Guo Meng 51 Alan Schatzberg 52 William Bunney 50 Jack Barchas 51 Edward Jones 53 Stanley Watson 54 Richard Myers 49 Huda Akil 54 Michael Boehnke 4 Kim Chambert 3 Jennifer Moran 3 Ed Scolnick 3 Srdjan Djurovic 5, 55 Ingrid Melle 5, 6 Gunnar Morken 56, 57 Michael Gill 10, 17 Derek Morris 17 Emma Quinn 1, 17 Thomas Mühleisen 7, 8 Franziska Degenhardt 7, 8 Manuel Mattheisen 20, 8 Johannes Schumacher 8 Wolfgang Maier 58 Michael Steffens 20 Peter Propping 8 Markus Nöthen 7, 8 Adebayo Anjorin 19 Nick Bass 19 Hugh Gurling 19 Radhika Kandaswamy 19 Jacob Lawrence 19 Kevin Mcghee 15, 16 Andrew Mcintosh 15, 16 Alan Mclean 15, 16 Walter Muir 15, 16 Benjamin Pickard 15, 16 Gerome Breen 42, 59 David St Clair 59 Sian Caesar 60 Katherine Gordon-Smith 10, 60 Lisa Jones 60 Christine Fraser 10 Elaine Green 10 Detelina Grozeva 10 Ian Jones 10 George Kirov 10 Valentina Moskvina 10, 26 Ivan Nikolov 1, 10 Michael O'Donovan 1, 10 Michael Owen 10 David Collier 42 Amanda Elkin 42 Richard Williamson 42 Allan Young 46, 61 I Nicol Ferrier 46 Kari Stefansson 62 Hreinn Stefansson 62 Porgeir Porgeirsson 62 Stacy Steinberg 62 Omar Gustafsson 62 Sarah Bergen 2, 3 Vishwajit Nimgaonkar 63 Christina Hultman 64 Mikael Landén 64, 65 Paul Lichtenstein 64 Patrick Sullivan 66 Martin Schalling 67 Urban Osby 67 Lena Backlund 68 Louise Frisén 67 Niklas Langstrom 65 Stéphane Jamain 69, 70, 71 Marion Leboyer 69, 70, 71 Bruno Etain 69, 70, 71 Frank Bellivier 69, 70, 71 Hannes Petursson 72 Engilbert Sigur Sson 72 Bertram Müller-Mysok 73 Susanne Lucae 73 Markus Schwarz 74 Peter Schofield 75, 76 Nick Martin 48 Grant Montgomery 48 Mark Lathrop 77 Högni Oskarsson 78 Michael Bauer 79 Adam Wright 80 Philip Mitchell 80 Martin Hautzinger 81 Andreas Reif 82 John Kelsoe 25, 83 Shaun Purcell 3, 2
* Auteur correspondant
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.
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Article dans une revue
Nature Genetics, Nature Publishing Group, 2011, 43 (10), pp.977-83. 〈10.1038/ng.943〉
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Pamela Sklar, Stephan Ripke, Laura Scott, Ole Andreassen, Sven Cichon, et al.. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.. Nature Genetics, Nature Publishing Group, 2011, 43 (10), pp.977-83. 〈10.1038/ng.943〉. 〈inserm-00634944〉

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