Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21926972
TITLE
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
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.
DATE PUBLISHED
2011 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/03/28
accepted 2011/08/23
aheadofprint 2011/09/18
entrez 2011/09/20 06:00
pubmed 2011/09/20 06:00
medline 2011/12/13 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Psychiatric GWAS Consortium Bipolar Disorder Working Group Division of Psychiatric Genomics, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA. pamela.sklar@mssm.edu
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Sklar Pamela P
Ripke Stephan S
Scott Laura J LJ
Andreassen Ole A OA
Cichon Sven S
Craddock Nick N
Edenberg Howard J HJ
Nurnberger John I JI
Rietschel Marcella M
Blackwood Douglas D
Corvin Aiden A
Flickinger Matthew M
Guan Weihua W
Mattingsdal Morten M
McQuillen Andrew A
Kwan Phoenix P
Wienker Thomas F TF
Daly Mark M
Dudbridge Frank F
Holmans Peter A PA
Lin Danyu D
Burmeister Margit M
Greenwood Tiffany A TA
Hamshere Marian L ML
Muglia Pierandrea P
Smith Erin N EN
Zandi Peter P PP
Nievergelt Caroline M CM
McKinney Rebecca R
Shilling Paul D PD
Schork Nicholas J NJ
Bloss Cinnamon S CS
Foroud Tiatiana T
Koller Daniel L DL
Gershon Elliot S ES
Liu Chunyu C
Badner Judith A JA
Scheftner William A WA
Lawson William B WB
Nwulia Evaristus A EA
Hipolito Maria M
Coryell William W
Rice John J
Byerley William W
McMahon Francis J FJ
Schulze Thomas G TG
Berrettini Wade W
Lohoff Falk W FW
Potash James B JB
Mahon Pamela B PB
McInnis Melvin G MG
Zöllner Sebastian S
Zhang Peng P
Craig David W DW
Szelinger Szabocls S
Barrett Thomas B TB
Breuer René R
Meier Sandra S
Strohmaier Jana J
Witt Stephanie H SH
Tozzi Federica F
Farmer Anne A
McGuffin Peter P
Strauss John J
Xu Wei W
Kennedy James L JL
Vincent John B JB
Matthews Keith K
Day Richard R
Ferreira Manuel A MA
O'Dushlaine Colm C
Perlis Roy R
Raychaudhuri Soumya S
Ruderfer Douglas D
Lee Phil H PH
Smoller Jordan W JW
Li Jun J
Absher Devin D
Bunny William E WE
Barchas Jack D JD
Schatzberg Alan F AF
Jones Edward G EG
Meng Fan F
Thompson Robert C RC
Watson Stanley J SJ
Myers Richard M RM
Akil Huda H
Boehnke Michael M
Chambert Kim K
Moran Jennifer J
Scolnick Ed E
Djurovic Srdjan S
Melle Ingrid I
Morken Gunnar G
Gill Michael M
Morris Derek D
Quinn Emma E
Mühleisen Thomas W TW
Degenhardt Franziska A FA
Mattheisen Manuel M
Schumacher Johannes J
Maier Wolfgang W
Steffans Michael M
Propping Peter P
Nöthen Markus M MM
Anjorin Adebayo A
Bass Nick N
Gurling Hugh H
Kandaswamy Radhika R
Lawrence Jacob J
McGhee Kevin K
McIntosh Andrew A
McLean Alan W AW
Muir Walter J WJ
Pickard Benjamin S BS
Breen Gerome G
St Clair David D
Caesar Sian S
Gordon-Smith Katherine K
Jones Lisa L
Fraser Christine C
Green Elaine K EK
Frozeva Detelina D
Jones Ian R IR
Kirov George G
Moskvina Valentina V
Nikolov Ivan I
O'Donovan Michael C MC
Owen Michael J MJ
Collier David A DA
Elkin Amanda A
Williamson Richard R
Young Allan H AH
Ferrier I Nicole IN
Stefansson Kari K
Stefansson Hreinn H
Porgeirsson Porgeir P
Steinberg Stacy S
Gustafsson Ómar
Bergen Sarah E SE
Nimgaonkar Vishwajit V
Hultman Christina C
Landén Mikael M
Lichtenstein Paul P
Sullivan Patrick P
Schalling Martin M
Osby Urban U
Backlund Lena L
Frisén Louise L
Langstrom Niklas N
Jamain Stéphane S
Leboyer Marion M
Etain Bruno B
Bellivier Frank F
Petursson Hannes H
Sigurđsson Engilbert E
Müller-Mysok Bertram B
Lucae Susanne S
Schwarz Markus M
Fullerton Janice M JM
Schofield Peter R PR
Martin Nick N
Montgomery Grant W GW
Lathrop Mark M
Óskarsson Högni H
Bauer Michael M
Wright Adam A
Mitchell Philip B PB
Hautzinger Martin M
Reif Andreas A
Kelsoe John R JR
Purcell Shaun M SM
JOURNAL
VOLUME: 43
ISSUE: 10
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2011
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Arch Gen Psychiatry. 1999 Feb;56(2):162-8 10025441
Cites Biometrics. 1999 Dec;55(4):997-1004 11315092
Cites J Med Genet. 2005 Mar;42(3):193-204 15744031
Cites Cell. 2006 Nov 3;127(3):591-606 17081980
Cites Nature. 2007 Jun 7;447(7145):661-78 17554300
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Am J Hum Genet. 2007 Nov;81(5):1084-97 17924348
Cites Mol Psychiatry. 2008 Feb;13(2):197-207 17486107
Cites Mol Psychiatry. 2008 Jun;13(6):558-69 18317468
Cites Mol Psychiatry. 2009 Jan;14(1):10-7 19002139
Cites Lancet. 2009 Jan 17;373(9659):234-9 19150704
Cites Nat Genet. 2008 Sep;40(9):1056-8 18711365
Cites Trends Genet. 2009 Feb;25(2):99-105 19144440
Cites Mol Psychiatry. 2009 Apr;14(4):376-80 19114987
Cites Mol Psychiatry. 2009 May;14(5):487-91 19088739
Cites Am J Psychiatry. 2009 May;166(5):540-56 19339359
Cites Proc Natl Acad Sci U S A. 2009 May 5;106(18):7501-6 19416921
Cites Mol Psychiatry. 2009 Aug;14(8):755-63 19488044
Cites Nature. 2009 Aug 6;460(7256):748-52 19571811
Cites Am J Psychiatry. 2009 Dec;166(12):1413-4 19952088
Cites Neuroimage. 2010 Jan 15;49(2):1831-6 19781653
Cites Mol Psychiatry. 2010 Feb;15(2):119-21 20098439
Cites Arch Gen Psychiatry. 2010 Aug;67(8):803-11 20679588
Cites J Affect Disord. 2010 Oct;126(1-2):312-6 20451256
Cites Arch Gen Psychiatry. 2010 Sep;67(9):939-45 20819988
Cites Mol Psychiatry. 2010 Oct;15(10):1016-22 19621016
Cites Psychiatr Genet. 2011 Feb;21(1):1-4 21057379
Cites Am J Hum Genet. 2011 Mar 11;88(3):372-81 21353194
Cites J Med Genet. 1999 Aug;36(8):585-94 10465107
Cites Bipolar Disord. 2000 Jun;2(2):108-19 11252650
ErratumIn Nat Genet. 2012 Sep;44(9):1072 11252650 Fullerton, Janice M [added]; Hyoun, Phil L [corrected to Lee, Phil H]; Meng, Fan Guo [corrected to Meng, Fan]
GRANTS
GRANTID AGENCY COUNTRY
1U54RR025204 NCRR NIH HHS United States
G0701003 Medical Research Council United Kingdom
G0701007 Medical Research Council United Kingdom
G1000708 Medical Research Council United Kingdom
G1000718 Medical Research Council United Kingdom
MH059567 NIMH NIH HHS United States
MH078151 NIMH NIH HHS United States
MH080372 NIMH NIH HHS United States
MH081804 NIMH NIH HHS United States
MH59553 NIMH NIH HHS United States
P50 MH066392 NIMH NIH HHS United States
R01 MH071681 NIMH NIH HHS United States
R01 MH074027 NIMH NIH HHS United States
R01 MH077139 NIMH NIH HHS United States
R01 MH080403 NIMH NIH HHS United States
R01 MH083738 NIMH NIH HHS United States
R01 MH093500-01 NIMH NIH HHS United States
U01 MH094421 NIMH NIH HHS United States
Intramural NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alleles
Bipolar Disorder genetics
Calcium Channels, L-Type metabolism
Case-Control Studies metabolism
Databases, Genetic metabolism
Genetic Loci metabolism
Genetic Predisposition to Disease metabolism
Genome, Human metabolism
Genome-Wide Association Study metabolism
Humans metabolism
Linkage Disequilibrium metabolism
Nuclear Proteins metabolism
Polymorphism, Single Nucleotide metabolism
Schizophrenia genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CACNA1C protein, human
0 Calcium Channels, L-Type
0 Nuclear Proteins
OTHER ID's
OTHERID SOURCE
HALMS634944 NLM
PMC3637176 NLM