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PMID |
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TITLE |
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Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. |
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ABSTRACT |
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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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DATE PUBLISHED |
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HISTORY |
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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 |
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AUTHORS |
|
NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
|
Psychiatric GWAS Consortium Bipolar Disorder Working Group |
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Division of Psychiatric Genomics, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA. pamela.sklar@mssm.edu |
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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 |
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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 |
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Akil |
Huda |
H |
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Boehnke |
Michael |
M |
|
Chambert |
Kim |
K |
|
Moran |
Jennifer |
J |
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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 |
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McGhee |
Kevin |
K |
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McIntosh |
Andrew |
A |
|
McLean |
Alan W |
AW |
|
Muir |
Walter J |
WJ |
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Pickard |
Benjamin S |
BS |
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Breen |
Gerome |
G |
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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 |
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Moskvina |
Valentina |
V |
|
Nikolov |
Ivan |
I |
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O'Donovan |
Michael C |
MC |
|
Owen |
Michael J |
MJ |
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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 |
Ó |
|
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 |
|
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JOURNAL |
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VOLUME: 43 |
ISSUE: 10 |
TITLE: Nature genetics |
ISOABBREVIATION: Nat. Genet. |
YEAR: 2011 |
MONTH: Oct |
DAY: |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1546-1718 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Nat Genet |
COUNTRY: United States |
ISSNLINKING: 1061-4036 |
NLMUNIQUEID: 9216904 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, N.I.H., Extramural |
Research Support, N.I.H., Intramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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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] |
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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 |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Alleles |
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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 |
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SUPPLEMENTARY MESH |
|
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GENE SYMBOLS |
|
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CHEMICALS |
|
REGISTRYNUMBER |
NAMEOFSUBSTANCE |
0 |
CACNA1C protein, human |
0 |
Calcium Channels, L-Type |
0 |
Nuclear Proteins |
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OTHER ID's |
|
OTHERID |
SOURCE |
HALMS634944 |
NLM |
PMC3637176 |
NLM |
|
|