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PMID |
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TITLE |
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Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. |
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ABSTRACT |
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We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)). |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2010/09/09 |
accepted |
2011/03/10 |
aheadofprint |
2011/04/03 |
entrez |
2011/04/05 06:00 |
pubmed |
2011/04/05 06:00 |
medline |
2011/07/02 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Hollingworth P |
|
Hollingworth |
Paul |
P |
|
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK. |
Harold D |
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Harold |
Denise |
D |
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Sims R |
|
Sims |
Rebecca |
R |
|
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Gerrish A |
|
Gerrish |
Amy |
A |
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Lambert JC |
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Lambert |
Jean-Charles |
JC |
|
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Carrasquillo MM |
|
Carrasquillo |
Minerva M |
MM |
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Abraham R |
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Abraham |
Richard |
R |
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Hamshere ML |
|
Hamshere |
Marian L |
ML |
|
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Pahwa JS |
|
Pahwa |
Jaspreet Singh |
JS |
|
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Moskvina V |
|
Moskvina |
Valentina |
V |
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Dowzell K |
|
Dowzell |
Kimberley |
K |
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Jones N |
|
Jones |
Nicola |
N |
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Stretton A |
|
Stretton |
Alexandra |
A |
|
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Thomas C |
|
Thomas |
Charlene |
C |
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Richards A |
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Richards |
Alex |
A |
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Ivanov D |
|
Ivanov |
Dobril |
D |
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Widdowson C |
|
Widdowson |
Caroline |
C |
|
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Chapman J |
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Chapman |
Jade |
J |
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Lovestone S |
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Lovestone |
Simon |
S |
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Powell J |
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Powell |
John |
J |
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Proitsi P |
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Proitsi |
Petroula |
P |
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Lupton MK |
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Lupton |
Michelle K |
MK |
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Brayne C |
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Brayne |
Carol |
C |
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Rubinsztein DC |
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Rubinsztein |
David C |
DC |
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Gill M |
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Gill |
Michael |
M |
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Lawlor B |
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Lawlor |
Brian |
B |
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Lynch A |
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Lynch |
Aoibhinn |
A |
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Brown KS |
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Brown |
Kristelle S |
KS |
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Passmore PA |
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Passmore |
Peter A |
PA |
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Craig D |
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Craig |
David |
D |
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McGuinness B |
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McGuinness |
Bernadette |
B |
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Todd S |
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Todd |
Stephen |
S |
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Holmes C |
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Holmes |
Clive |
C |
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Mann D |
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Mann |
David |
D |
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Smith AD |
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Smith |
A David |
AD |
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Beaumont H |
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Beaumont |
Helen |
H |
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Warden D |
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Warden |
Donald |
D |
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Wilcock G |
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Wilcock |
Gordon |
G |
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Love S |
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Love |
Seth |
S |
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Kehoe PG |
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Kehoe |
Patrick G |
PG |
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Hooper NM |
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Hooper |
Nigel M |
NM |
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Vardy ER |
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Vardy |
Emma R L C |
ER |
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Hardy J |
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Hardy |
John |
J |
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Mead S |
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Mead |
Simon |
S |
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Fox NC |
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Fox |
Nick C |
NC |
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Rossor M |
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Rossor |
Martin |
M |
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Collinge J |
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Collinge |
John |
J |
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Maier W |
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Maier |
Wolfgang |
W |
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Jessen F |
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Jessen |
Frank |
F |
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Rüther E |
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Rüther |
Eckart |
E |
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Schürmann B |
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Schürmann |
Britta |
B |
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Heun R |
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Heun |
Reiner |
R |
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Kölsch H |
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Kölsch |
Heike |
H |
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van den Bussche H |
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van den Bussche |
Hendrik |
H |
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Heuser I |
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Heuser |
Isabella |
I |
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Kornhuber J |
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Kornhuber |
Johannes |
J |
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Wiltfang J |
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Wiltfang |
Jens |
J |
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Dichgans M |
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Dichgans |
Martin |
M |
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Frölich L |
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Frölich |
Lutz |
L |
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Hampel H |
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Hampel |
Harald |
H |
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Gallacher J |
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Gallacher |
John |
J |
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Hüll M |
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Hüll |
Michael |
M |
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Rujescu D |
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Rujescu |
Dan |
D |
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Giegling I |
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Giegling |
Ina |
I |
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Goate AM |
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Goate |
Alison M |
AM |
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Kauwe JS |
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Kauwe |
John S K |
JS |
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Cruchaga C |
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Cruchaga |
Carlos |
C |
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Nowotny P |
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Nowotny |
Petra |
P |
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Morris JC |
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Morris |
John C |
JC |
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Mayo K |
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Mayo |
Kevin |
K |
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Sleegers K |
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Sleegers |
Kristel |
K |
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Bettens K |
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Bettens |
Karolien |
K |
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Engelborghs S |
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Engelborghs |
Sebastiaan |
S |
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De Deyn PP |
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De Deyn |
Peter P |
PP |
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Van Broeckhoven C |
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Van Broeckhoven |
Christine |
C |
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Livingston G |
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Livingston |
Gill |
G |
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Bass NJ |
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Bass |
Nicholas J |
NJ |
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Gurling H |
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Gurling |
Hugh |
H |
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McQuillin A |
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McQuillin |
Andrew |
A |
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Gwilliam R |
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Gwilliam |
Rhian |
R |
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Deloukas P |
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Deloukas |
Panagiotis |
P |
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Al-Chalabi A |
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Al-Chalabi |
Ammar |
A |
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Shaw CE |
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Shaw |
Christopher E |
CE |
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Tsolaki M |
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Tsolaki |
Magda |
M |
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Singleton AB |
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Singleton |
Andrew B |
AB |
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Guerreiro R |
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Guerreiro |
Rita |
R |
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Mühleisen TW |
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Mühleisen |
Thomas W |
TW |
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Nöthen MM |
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Nöthen |
Markus M |
MM |
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Moebus S |
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Moebus |
Susanne |
S |
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Jöckel KH |
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Jöckel |
Karl-Heinz |
KH |
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Klopp N |
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Klopp |
Norman |
N |
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Wichmann HE |
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Wichmann |
H-Erich |
HE |
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Pankratz VS |
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Pankratz |
V Shane |
VS |
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Sando SB |
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Sando |
Sigrid B |
SB |
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Aasly JO |
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Aasly |
Jan O |
JO |
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Barcikowska M |
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Barcikowska |
Maria |
M |
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Wszolek ZK |
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Wszolek |
Zbigniew K |
ZK |
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Dickson DW |
|
Dickson |
Dennis W |
DW |
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Graff-Radford NR |
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Graff-Radford |
Neill R |
NR |
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Petersen RC |
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Petersen |
Ronald C |
RC |
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Alzheimer's Disease Neuroimaging Initiative |
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van Duijn CM |
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van Duijn |
Cornelia M |
CM |
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Breteler MM |
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Breteler |
Monique M B |
MM |
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Ikram MA |
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Ikram |
M Arfan |
MA |
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DeStefano AL |
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DeStefano |
Anita L |
AL |
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Fitzpatrick AL |
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Fitzpatrick |
Annette L |
AL |
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Lopez O |
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Lopez |
Oscar |
O |
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Launer LJ |
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Launer |
Lenore J |
LJ |
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Seshadri S |
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Seshadri |
Sudha |
S |
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CHARGE consortium |
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Berr C |
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Berr |
Claudine |
C |
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Campion D |
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Campion |
Dominique |
D |
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Epelbaum J |
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Epelbaum |
Jacques |
J |
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Dartigues JF |
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Dartigues |
Jean-François |
JF |
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Tzourio C |
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Tzourio |
Christophe |
C |
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Alpérovitch A |
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Alpérovitch |
Annick |
A |
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Lathrop M |
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Lathrop |
Mark |
M |
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EADI1 consortium |
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Feulner TM |
|
Feulner |
Thomas M |
TM |
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Friedrich P |
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Friedrich |
Patricia |
P |
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Riehle C |
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Riehle |
Caterina |
C |
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Krawczak M |
|
Krawczak |
Michael |
M |
|
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Schreiber S |
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Schreiber |
Stefan |
S |
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Mayhaus M |
|
Mayhaus |
Manuel |
M |
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Nicolhaus S |
|
Nicolhaus |
S |
S |
|
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Wagenpfeil S |
|
Wagenpfeil |
Stefan |
S |
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Steinberg S |
|
Steinberg |
Stacy |
S |
|
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Stefansson H |
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Stefansson |
Hreinn |
H |
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Stefansson K |
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Stefansson |
Kari |
K |
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Snaedal J |
|
Snaedal |
Jon |
J |
|
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Björnsson S |
|
Björnsson |
Sigurbjörn |
S |
|
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Jonsson PV |
|
Jonsson |
Palmi V |
PV |
|
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Chouraki V |
|
Chouraki |
Vincent |
V |
|
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Genier-Boley B |
|
Genier-Boley |
Benjamin |
B |
|
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Hiltunen M |
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Hiltunen |
Mikko |
M |
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Soininen H |
|
Soininen |
Hilkka |
H |
|
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Combarros O |
|
Combarros |
Onofre |
O |
|
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Zelenika D |
|
Zelenika |
Diana |
D |
|
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Delepine M |
|
Delepine |
Marc |
M |
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Bullido MJ |
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Bullido |
Maria J |
MJ |
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Pasquier F |
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Pasquier |
Florence |
F |
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Mateo I |
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Mateo |
Ignacio |
I |
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Frank-Garcia A |
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Frank-Garcia |
Ana |
A |
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Porcellini E |
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Porcellini |
Elisa |
E |
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Hanon O |
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Hanon |
Olivier |
O |
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Coto E |
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Coto |
Eliecer |
E |
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Alvarez V |
|
Alvarez |
Victoria |
V |
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Bosco P |
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Bosco |
Paolo |
P |
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Siciliano G |
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Siciliano |
Gabriele |
G |
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Mancuso M |
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Mancuso |
Michelangelo |
M |
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Panza F |
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Panza |
Francesco |
F |
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Solfrizzi V |
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Solfrizzi |
Vincenzo |
V |
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Nacmias B |
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Nacmias |
Benedetta |
B |
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Sorbi S |
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Sorbi |
Sandro |
S |
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Bossù P |
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Bossù |
Paola |
P |
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Piccardi P |
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Piccardi |
Paola |
P |
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Arosio B |
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Arosio |
Beatrice |
B |
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Annoni G |
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Annoni |
Giorgio |
G |
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Seripa D |
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Seripa |
Davide |
D |
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Pilotto A |
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Pilotto |
Alberto |
A |
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Scarpini E |
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Scarpini |
Elio |
E |
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Galimberti D |
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Galimberti |
Daniela |
D |
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Brice A |
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Brice |
Alexis |
A |
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Hannequin D |
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Hannequin |
Didier |
D |
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Licastro F |
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Licastro |
Federico |
F |
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Jones L |
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Jones |
Lesley |
L |
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Holmans PA |
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Holmans |
Peter A |
PA |
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Jonsson T |
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Jonsson |
Thorlakur |
T |
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Riemenschneider M |
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Riemenschneider |
Matthias |
M |
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Morgan K |
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Morgan |
Kevin |
K |
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Younkin SG |
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Younkin |
Steven G |
SG |
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Owen MJ |
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Owen |
Michael J |
MJ |
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O'Donovan M |
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O'Donovan |
Michael |
M |
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Amouyel P |
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Amouyel |
Philippe |
P |
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Williams J |
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Williams |
Julie |
J |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 43 |
ISSUE: 5 |
TITLE: Nature genetics |
ISOABBREVIATION: Nat. Genet. |
YEAR: 2011 |
MONTH: May |
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 |
Meta-Analysis |
Research Support, N.I.H., Extramural |
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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GRANTS |
|
GRANTID |
AGENCY |
COUNTRY |
082604 |
Wellcome Trust |
United Kingdom |
G0300429 |
Medical Research Council |
United Kingdom |
G0601846 |
Medical Research Council |
United Kingdom |
G0701075 |
Medical Research Council |
United Kingdom |
G0802189 |
Medical Research Council |
United Kingdom |
G0900688 |
Medical Research Council |
United Kingdom |
G0902227 |
Medical Research Council |
United Kingdom |
G9810900 |
Medical Research Council |
United Kingdom |
MC_G1000734 |
Medical Research Council |
United Kingdom |
MC_U123160651 |
Medical Research Council |
United Kingdom |
U24 AG021886 |
NIA NIH HHS |
United States |
|
Medical Research Council |
United Kingdom |
|
Wellcome Trust |
United Kingdom |
|
GENERAL NOTE |
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KEYWORDS |
|
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MESH HEADINGS |
|
DESCRIPTORNAME |
QUALIFIERNAME |
ATP-Binding Cassette Transporters |
genetics |
Adaptor Proteins, Signal Transducing |
genetics |
Aged |
genetics |
Aged, 80 and over |
genetics |
Alzheimer Disease |
genetics |
Antigens, CD |
genetics |
Antigens, Differentiation, Myelomonocytic |
genetics |
Case-Control Studies |
genetics |
Cytoskeletal Proteins |
genetics |
Databases, Genetic |
genetics |
Female |
genetics |
Genetic Predisposition to Disease |
genetics |
Genetic Variation |
genetics |
Genome-Wide Association Study |
genetics |
Humans |
genetics |
Male |
genetics |
Membrane Proteins |
genetics |
Multigene Family |
genetics |
Polymorphism, Single Nucleotide |
genetics |
Receptor, EphA1 |
genetics |
Sialic Acid Binding Ig-like Lectin 3 |
genetics |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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REGISTRYNUMBER |
NAMEOFSUBSTANCE |
0 |
ABCA7 protein, human |
0 |
Adaptor Proteins, Signal Transducing |
0 |
Antigens, CD |
0 |
Antigens, Differentiation, Myelomonocytic |
0 |
CD2-associated protein |
0 |
CD33 protein, human |
0 |
Cytoskeletal Proteins |
0 |
MS4A4E protein, human |
0 |
Membrane Proteins |
0 |
Sialic Acid Binding Ig-like Lectin 3 |
EC 2.7.10.1 |
Receptor, EphA1 |
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OTHER ID's |
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OTHERID |
SOURCE |
PMC3084173 |
NLM |
UKMS34702 |
NLM |
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