|
|
| PMID |
|
|
| TITLE |
|
| Genome-wide association study identifies five new schizophrenia loci. |
|
| ABSTRACT |
|
|
|
| We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)). |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2011/02/16 |
| accepted |
2011/08/19 |
| 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 |
|
Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium |
|
|
|
|
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. |
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Ripke |
Stephan |
S |
|
| Sanders |
Alan R |
AR |
|
| Kendler |
Kenneth S |
KS |
|
| Levinson |
Douglas F |
DF |
|
| Sklar |
Pamela |
P |
|
| Holmans |
Peter A |
PA |
|
| Lin |
Dan-Yu |
DY |
|
| Duan |
Jubao |
J |
|
| Ophoff |
Roel A |
RA |
|
| Andreassen |
Ole A |
OA |
|
| Scolnick |
Edward |
E |
|
| Cichon |
Sven |
S |
|
| St Clair |
David |
D |
|
| Corvin |
Aiden |
A |
|
| Gurling |
Hugh |
H |
|
| Werge |
Thomas |
T |
|
| Rujescu |
Dan |
D |
|
| Blackwood |
Douglas H R |
DH |
|
| Pato |
Carlos N |
CN |
|
| Malhotra |
Anil K |
AK |
|
| Purcell |
Shaun |
S |
|
| Dudbridge |
Frank |
F |
|
| Neale |
Benjamin M |
BM |
|
| Rossin |
Lizzy |
L |
|
| Visscher |
Peter M |
PM |
|
| Posthuma |
Danielle |
D |
|
| Ruderfer |
Douglas M |
DM |
|
| Fanous |
Ayman |
A |
|
| Stefansson |
Hreinn |
H |
|
| Steinberg |
Stacy |
S |
|
| Mowry |
Bryan J |
BJ |
|
| Golimbet |
Vera |
V |
|
| De Hert |
Marc |
M |
|
| Jönsson |
Erik G |
EG |
|
| Bitter |
István |
I |
|
| Pietiläinen |
Olli P H |
OP |
|
| Collier |
David A |
DA |
|
| Tosato |
Sarah |
S |
|
| Agartz |
Ingrid |
I |
|
| Albus |
Margot |
M |
|
| Alexander |
Madeline |
M |
|
| Amdur |
Richard L |
RL |
|
| Amin |
Farooq |
F |
|
| Bass |
Nicholas |
N |
|
| Bergen |
Sarah E |
SE |
|
| Black |
Donald W |
DW |
|
| Børglum |
Anders D |
AD |
|
| Brown |
Matthew A |
MA |
|
| Bruggeman |
Richard |
R |
|
| Buccola |
Nancy G |
NG |
|
| Byerley |
William F |
WF |
|
| Cahn |
Wiepke |
W |
|
| Cantor |
Rita M |
RM |
|
| Carr |
Vaughan J |
VJ |
|
| Catts |
Stanley V |
SV |
|
| Choudhury |
Khalid |
K |
|
| Cloninger |
C Robert |
CR |
|
| Cormican |
Paul |
P |
|
| Craddock |
Nicholas |
N |
|
| Danoy |
Patrick A |
PA |
|
| Datta |
Susmita |
S |
|
| de Hann |
Lieuwe |
L |
|
| Demontis |
Ditte |
D |
|
| Dikeos |
Dimitris |
D |
|
| Djurovic |
Srdjan |
S |
|
| Donnelly |
Peter |
P |
|
| Donohoe |
Gary |
G |
|
| Duong |
Linh |
L |
|
| Dwyer |
Sarah |
S |
|
| Fink-Jensen |
Anders |
A |
|
| Freedman |
Robert |
R |
|
| Freimer |
Nelson B |
NB |
|
| Friedl |
Marion |
M |
|
| Georgieva |
Lydmila |
L |
|
| Giegling |
Ina |
I |
|
| Gill |
Michael |
M |
|
| Glenthøj |
Birte |
B |
|
| Godard |
Stephanie |
S |
|
| Hamshere |
Marian |
M |
|
| Hansen |
Mark |
M |
|
| Hansen |
Thomas |
T |
|
| Hartmann |
Annette M |
AM |
|
| Henskens |
Frans A |
FA |
|
| Hougaard |
David M |
DM |
|
| Hultman |
Christina M |
CM |
|
| Ingason |
Andrés |
A |
|
| Jablensky |
Assen V |
AV |
|
| Jakobsen |
Klaus D |
KD |
|
| Jay |
Maurice |
M |
|
| Jürgens |
Gesche |
G |
|
| Kahn |
René S |
RS |
|
| Keller |
Mathhew C |
MC |
|
| Kenis |
Gunter |
G |
|
| Kenny |
Elaine |
E |
|
| Kim |
Yunjung |
Y |
|
| Kirov |
George K |
GK |
|
| Konnerth |
Heike |
H |
|
| Konte |
Bettina |
B |
|
| Krabbendam |
Lydia |
L |
|
| Krausucki |
Robert |
R |
|
| Lasseter |
Virginia K |
VK |
|
| Laurent |
Claudine |
C |
|
| Lawrence |
Jacob |
J |
|
| Lencz |
Todd |
T |
|
| Lerer |
F Bernard |
FB |
|
| Liang |
Kung-Yee |
KY |
|
| Lichtenstein |
Paul |
P |
|
| Lieberman |
Jeffrey A |
JA |
|
| Linszen |
Don H |
DH |
|
| Lönnqvist |
Jouko |
J |
|
| Loughland |
Carmel M |
CM |
|
| Maclean |
Alan W |
AW |
|
| Maher |
Brion S |
BS |
|
| Maier |
Wolfgang |
W |
|
| Mallet |
Jacques |
J |
|
| Malloy |
Pat |
P |
|
| Mattheisen |
Manuel |
M |
|
| Mattinsgsdal |
Morten |
M |
|
| McGhee |
Kevin A |
KA |
|
| McGrath |
John J |
JJ |
|
| McIntosh |
Andrew |
A |
|
| McLean |
Duncan E |
DE |
|
| McQuillin |
Andrew |
A |
|
| Melle |
Ingrid |
I |
|
| Michie |
Patricia T |
PT |
|
| Milanova |
Vihra |
V |
|
| Morris |
Derek W |
DW |
|
| Mors |
Ole |
O |
|
| Mortensen |
Preben B |
PB |
|
| Moskvina |
Valentina |
V |
|
| Muglia |
Pierandrea |
P |
|
| Myin-Germeys |
Inez |
I |
|
| Nertney |
Deborah A |
DA |
|
| Nestadt |
Gerald |
G |
|
| Nielsen |
Jimmi |
J |
|
| Nikolov |
Ivan |
I |
|
| Nordentroft |
Merete |
M |
|
| Norton |
Nadine |
N |
|
| Nöthen |
Markus M |
MM |
|
| O'Dushlaine |
Colm T |
CT |
|
| Olincy |
Ann |
A |
|
| Olsen |
Line |
L |
|
| O'Neill |
F Anthony |
FA |
|
| Ørntoft |
Torben |
T |
|
| Owen |
Michael J |
MJ |
|
| Pantelis |
Christos |
C |
|
| Papadimitriou |
George |
G |
|
| Pato |
Michele T |
MT |
|
| Peltonen |
Leena |
L |
|
| Petursson |
Hannes |
H |
|
| Pickard |
Ben |
B |
|
| Pimm |
Jonathan |
J |
|
| Pulver |
Ann E |
AE |
|
| Puri |
Vinay |
V |
|
| Quested |
Digby |
D |
|
| Quinn |
Emma M |
EM |
|
| Rasmussen |
Henrik B |
HB |
|
| Réthelyi |
János M |
JM |
|
| Ribble |
Robert |
R |
|
| Rietschel |
Marcella |
M |
|
| Riley |
Brien P |
BP |
|
| Ruggeri |
Mirella |
M |
|
| Schall |
Ulrich |
U |
|
| Schulze |
Thomas G |
TG |
|
| Schwab |
Sibylle G |
SG |
|
| Scott |
Rodney J |
RJ |
|
| Shi |
Jianxin |
J |
|
| Sigurdsson |
Engilbert |
E |
|
| Silverman |
Jeremy M |
JM |
|
| Spencer |
Chris C A |
CC |
|
| Stefansson |
Kari |
K |
|
| Strange |
Amy |
A |
|
| Strengman |
Eric |
E |
|
| Stroup |
T Scott |
TS |
|
| Suvisaari |
Jaana |
J |
|
| Tereniuis |
Lars |
L |
|
| Thirumalai |
Srinivasa |
S |
|
| Thygesen |
Johan H |
JH |
|
| Timm |
Sally |
S |
|
| Toncheva |
Draga |
D |
|
| van den Oord |
Edwin |
E |
|
| van Os |
Jim |
J |
|
| van Winkel |
Ruud |
R |
|
| Veldink |
Jan |
J |
|
| Walsh |
Dermot |
D |
|
| Wang |
August G |
AG |
|
| Wiersma |
Durk |
D |
|
| Wildenauer |
Dieter B |
DB |
|
| Williams |
Hywel J |
HJ |
|
| Williams |
Nigel M |
NM |
|
| Wormley |
Brandon |
B |
|
| Zammit |
Stan |
S |
|
| Sullivan |
Patrick F |
PF |
|
| O'Donovan |
Michael C |
MC |
|
| Daly |
Mark J |
MJ |
|
| Gejman |
Pablo V |
PV |
|
|
| 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, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 090532 |
Wellcome Trust |
United Kingdom |
| G0800509 |
Medical Research Council |
United Kingdom |
| G1000708 |
Medical Research Council |
United Kingdom |
| G1000718 |
Medical Research Council |
United Kingdom |
| K01 MH085812 |
NIMH NIH HHS |
United States |
| K23 MH001760 |
NIMH NIH HHS |
United States |
| P01 CA142538 |
NCI NIH HHS |
United States |
| P30 MH074543 |
NIMH NIH HHS |
United States |
| P50 MH066392 |
NIMH NIH HHS |
United States |
| R01 CA082659 |
NCI NIH HHS |
United States |
| R01 CA082659-12 |
NCI NIH HHS |
United States |
| R01 MH052618 |
NIMH NIH HHS |
United States |
| R01 MH058693 |
NIMH NIH HHS |
United States |
| R01 MH059565 |
NIMH NIH HHS |
United States |
| R01 MH059566 |
NIMH NIH HHS |
United States |
| R01 MH059586 |
NIMH NIH HHS |
United States |
| R01 MH059587 |
NIMH NIH HHS |
United States |
| R01 MH059588 |
NIMH NIH HHS |
United States |
| R01 MH060870 |
NIMH NIH HHS |
United States |
| R01 MH060879 |
NIMH NIH HHS |
United States |
| R01 MH061675 |
NIMH NIH HHS |
United States |
| R01 MH061884 |
NIMH NIH HHS |
United States |
| R01 MH062276 |
NIMH NIH HHS |
United States |
| R01 MH067257 |
NIMH NIH HHS |
United States |
| R01 MH068881 |
NIMH NIH HHS |
United States |
| R01 MH068921 |
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 MH078075 |
NIMH NIH HHS |
United States |
| R01 MH079800 |
NIMH NIH HHS |
United States |
| R01 MH080403 |
NIMH NIH HHS |
United States |
| R01 MH083094 |
NIMH NIH HHS |
United States |
| R01 MH084098 |
NIMH NIH HHS |
United States |
| R01 MH085548 |
NIMH NIH HHS |
United States |
| R37 GM047845 |
NIGMS NIH HHS |
United States |
| R37 GM047845-21 |
NIGMS NIH HHS |
United States |
| T32 GM007753 |
NIGMS NIH HHS |
United States |
| U01 MH046276 |
NIMH NIH HHS |
United States |
| U01 MH046289 |
NIMH NIH HHS |
United States |
| U01 MH046318 |
NIMH NIH HHS |
United States |
| U01 MH079470 |
NIMH NIH HHS |
United States |
| U01 MH085515 |
NIMH NIH HHS |
United States |
| U01 MH085518 |
NIMH NIH HHS |
United States |
| U01 MH085520 |
NIMH NIH HHS |
United States |
| U01 MH094421 |
NIMH NIH HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Alleles |
|
| Bipolar Disorder |
|
| Case-Control Studies |
|
| European Continental Ancestry Group |
|
| Female |
|
| Gene Dosage |
|
| Gene Expression Regulation |
|
| Genetic Loci |
|
| Genetic Predisposition to Disease |
|
| Genome, Human |
|
| Genome-Wide Association Study |
|
| Haplotypes |
|
| Humans |
|
| Linkage Disequilibrium |
|
| Logistic Models |
|
| Male |
|
| MicroRNAs |
metabolism |
| Mutation |
metabolism |
| Polymorphism, Single Nucleotide |
metabolism |
| Schizophrenia |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
MicroRNAs |
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| NIHMS360727 |
NLM |
| PMC3303194 |
NLM |
|
|
