Journal articles

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 J. Scott ⁴ Ole A. Andreassen ^{5, 6} Sven Cichon ^{7, 8, 9} Nick Craddock ¹⁰ Howard J. Edenberg ¹¹ John I. 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 F. Wienker ²⁰ Mark Daly ^{2, 3} Frank Dudbridge ²¹ Peter A. Holmans ^{10, 22} Danyu Lin ²³ Margit Burmeister ²⁴ Tiffany A. Greenwood ²⁵ Marian L. Hamshere ^{10, 26} Pierandrea Muglia ²⁶ Erin N. Smith ²⁷ Peter P. Zandi ²⁸ Caroline M. Nievergelt ²⁵ Rebecca Mckinney ²⁵ Paul D. Shilling ²⁵ Nicholas J. Schork ²⁹ Cinnamon S. Bloss ²⁷ Tatiana Foroud ¹² Daniel L. Koller ¹² Elliot S. Gershon ³⁰ Chunyu Liu ³⁰ Judith A. Badner ³⁰ William A. Scheftner ³¹ William B. Lawson ³² Evaristus A. Nwulia ³² Maria Hipolito ³² William Coryell ³³ John P. Rice ³⁴ William Byerley ³⁵ Francis J. Mcmahon ³⁶ Thomas G. Schulze ^{14, 36, 37} Wade Berrettini ³⁸ Falk W. Lohoff ³⁸ James B. Potash ²⁸ Pamela B. Mahon ²⁸ Melvin G. Mcinnis ³⁹ Sebastian Zöllner ³⁹ Peng Zhang ³⁹ David W. Craig ⁴⁰ Szabocls Szelinger ⁴⁰ Thomas B. Barrett ⁴¹ René Breuer ¹⁴ Sandra Meier ¹⁴ Jana Strohmaier ¹⁴ Stephanie H. Witt ¹⁴ Federica Tozzi ²⁶ Anne Farmer ⁴² Peter Mcguffin ⁴² John Strauss ⁴³ Wei Xu ⁴⁴ James L. Kennedy ⁴⁵ John B. Vincent ⁴³ Keith Matthews ⁴⁶ Richard Day ⁴⁷ Manuel D.C. Ferreira ^{2, 3, 48} Colm O'Dushlaine ^{2, 3} Roy Perlis ^{2, 3} Soumya Raychaudhuri ^{2, 3} Douglas Ruderfer ^{2, 3} Phil L. Hyoun ² Jordan W. Smoller ^{3, 2} Jun Li ²⁴ Devin Absher ⁴⁹ Robert C. Thompson ⁵⁰ Fan Guo Meng ⁵¹ Alan F. Schatzberg ⁵² William E. Bunney ⁵⁰ Jack D. Barchas ⁵¹ Edward G. Jones ⁵³ Stanley J. Watson ⁵⁴ Richard M. 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 W. Mühleisen ^{7, 8} Franziska A. Degenhardt ^{7, 8} Manuel Mattheisen ^{20, 8} Johannes Schumacher ⁸ Wolfgang Maier ⁵⁸ Michael Steffens ²⁰ Peter Propping ⁸ Markus M. 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 W. Mclean ^{15, 16} Walter J. Muir ^{15, 16} Benjamin S. 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 K. Green ¹⁰ Detelina Grozeva ¹⁰ Ian R. Jones ¹⁰ George Kirov ¹⁰ Valentina Moskvina ^{10, 26} Ivan Nikolov ^{1, 10} Michael C. O'Donovan ^{1, 10} Michael J. Owen ¹⁰ David A. Collier ⁴² Amanda Elkin ⁴² Richard Williamson ⁴² Allan H. young ^{46, 61} I Nicol Ferrier ⁴⁶ Kari Stefansson ⁶² Hreinn Stefansson ⁶² Porgeir Porgeirsson ⁶² Stacy Steinberg ⁶² Omar Gustafsson ⁶² Sarah E. 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 R. Schofield ^{75, 76} Nick Martin ⁴⁸ Grant W. Montgomery ⁴⁸ Mark Lathrop ⁷⁷ Högni Oskarsson ⁷⁸ Michael Bauer ⁷⁹ Adam Wright ⁸⁰ Philip B. Mitchell ⁸⁰ Martin Hautzinger ⁸¹ Andreas Reif ⁸² John R. Kelsoe ^{25, 83} Shaun M. Purcell ^{3, 2}

* Corresponding author

1 Division of Psychiatric Genomics

2 Center for Human Genetic Research

3 Stanley Center for Psychiatric Research

4 Department of Biostatistics and Center for Statistical Genetics

5 Institute of Clinical Medicine [Oslo]

6 Division of Mental Health and Addiction

7 Department of Genomics, Life and Brain Center

8 Institute of Human Genetics

9 INM-1 - Institute of Neuroscience and Medicine

10 MRC Centre for Neuropsychiatric Genetics and Genomics

11 Department of Biochemistry and Molecular Biology, Department of Medical and Molecular Genetics

12 Department of Psychiatry

13 Department of Medical and Molecular Genetics

14 Department of Genetic Epidemiology in Psychiatry [Mannhein]

15 Division of Psychiatry

16 Medical Genetics Section

17 Neuropsychiatric Genetics Research Group

18 Sorlandet Hospital HF

19 Department of Psychiatry and Behavioral Sciences

20 Department of Biomedicine and the Centre for Integrative Sequencing

21 LSHTM - London School of Hygiene and Tropical Medicine

22 Biostatistics and Bioinformatics Unit

23 Department of Biostatistics

24 Department of Human Genetics, Department of Psychiatry

25 Department of Psychiatry

26 Neurosciences Centre of Excellence in Drug Discovery

27 The Scripps Translational Science Institute and Scripps Health

28 Department of Mental Health

29 The Scripps Translational Science Institute and The Scripps Research Institute

30 McKusick-Nathans Institute of Genetic Medicine

31 Rush University Medical Center [Chicago]

32 Department of Psychiatry and Behavioral Sciences

33 Department of Psychiatry

34 WUSTL - Washington University in Saint Louis

35 Department of Psychiatry

36 Unit on the Genetic Basis of Mood and Anxiety Disorders

37 Department of Psychiatry and Psychotherapy

38 Department of Psychiatry [Philadelphia]

39 Department of Psychiatry

40 TGen - The Translational Genomics Research Institute

41 Internal Medicine

42 SGDP - Social, Genetic and Developmental Psychiatry Centre

43 Molecular Neuropsychiatry and Development Laboratory

44 Department of Biostatistics

45 Psychiatric Neurogenetics Section

46 University of Dundee School of Medicine

47 School of Neurology, Neurobiology and Psychiatry

48 Queensland Institute of Medical Research

49 HudsonAlpha Institute for Biotechnology [Huntsville, AL]

50 Department of Psychiatry and Human Behavior

51 Department of Psychiatry

52 Department of Psychiatry and Behavioral Sciences [Stanford]

53 Department of Psychiatry and Behavioral Sciences

54 Molecular Psychiatry Laboratory

55 Deparment of Medical Genetics

56 Department of Psychiatry

57 Department of Neuroscience

58 Department of Psychiatry and Psychotherapy

59 Institute of Medical Sciences

60 Department of Psychiatry, School of Clinical and Experimental Medicine

61 Institute of Mental Health

62 deCODE Genetics

63 Department of Human Genetics

64 MEB - Department of Medical Epidemiology and Biostatistics

65 Insitute of Neuroscience and Physiology

66 Medstar Research Institute

67 Department of Molecular Medicine

68 Department of Psychiatry

69 IMRB - Institut Mondor de Recherche Biomédicale

70 Service de psychiatrie

71 ENBREC - European Network of Bipolar Research Expert Centres

72 Division of Psychiatry

73 Max Planck Institute of Psychiatry

74 Psychiatric Center Nordbaden

75 Prince of Wales Medical Research Institute

76 UNSW - University of New South Wales [Sydney]

77 CNG - Centre National de Génotypage

78 Therapeia

79 Department of Psychiatry and Psychotherapy, ENBREC Group

80 School of Psychiatry

81 Department of Clinical and Developmental Psychology

82 Department of Psychiatry

83 Department of Psychiatry, Special Treatment and Evaluation Program (STEP)

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Biochemistry, Molecular Biology

Complete list of metadata

Cited literature [29 references] Display Hide Download

https://www.hal.inserm.fr/inserm-00634944
Contributor : Georges Guellaen Connect in order to contact the contributor
Submitted on : Friday, February 17, 2012 - 4:23:38 PM
Last modification on : Wednesday, May 4, 2022 - 3:29:37 AM
Long-term archiving on: : Thursday, November 22, 2012 - 12:56:02 PM