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GWAS Study

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.

Naj AC, Jun G, Beecham GW et al.

21460841 PubMed ID
GWAS Study Type
54429 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

NA
Naj AC
JG
Jun G
BG
Beecham GW
WL
Wang LS
VB
Vardarajan BN
BJ
Buros J
GP
Gallins PJ
BJ
Buxbaum JD
JG
Jarvik GP
CP
Crane PK
LE
Larson EB
BT
Bird TD
BB
Boeve BF
GN
Graff-Radford NR
DJ
De Jager PL
ED
Evans D
SJ
Schneider JA
CM
Carrasquillo MM
EN
Ertekin-Taner N
YS
Younkin SG
CC
Cruchaga C
KJ
Kauwe JS
NP
Nowotny P
KP
Kramer P
HJ
Hardy J
HM
Huentelman MJ
MA
Myers AJ
BM
Barmada MM
DF
Demirci FY
BC
Baldwin CT
GR
Green RC
RE
Rogaeva E
SG
St George-Hyslop P
AS
Arnold SE
BR
Barber R
BT
Beach T
BE
Bigio EH
BJ
Bowen JD
BA
Boxer A
BJ
Burke JR
CN
Cairns NJ
CC
Carlson CS
CR
Carney RM
CS
Carroll SL
CH
Chui HC
CD
Clark DG
CJ
Corneveaux J
CC
Cotman CW
CJ
Cummings JL
DC
DeCarli C
DS
DeKosky ST
DR
Diaz-Arrastia R
DM
Dick M
DD
Dickson DW
EW
Ellis WG
FK
Faber KM
FK
Fallon KB
FM
Farlow MR
FS
Ferris S
FM
Frosch MP
GD
Galasko DR
GM
Ganguli M
GM
Gearing M
GD
Geschwind DH
GB
Ghetti B
GJ
Gilbert JR
GS
Gilman S
GB
Giordani B
GJ
Glass JD
GJ
Growdon JH
HR
Hamilton RL
HL
Harrell LE
HE
Head E
HL
Honig LS
HC
Hulette CM
HB
Hyman BT
JG
Jicha GA
JL
Jin LW
JN
Johnson N
KJ
Karlawish J
KA
Karydas A
KJ
Kaye JA
KR
Kim R
KE
Koo EH
KN
Kowall NW
LJ
Lah JJ
LA
Levey AI
LA
Lieberman AP
LO
Lopez OL
MW
Mack WJ
MD
Marson DC
MF
Martiniuk F
MD
Mash DC
ME
Masliah E
MW
McCormick WC
MS
McCurry SM
MA
McDavid AN
MA
McKee AC
MM
Mesulam M
MB
Miller BL
MC
Miller CA
MJ
Miller JW
PJ
Parisi JE
PD
Perl DP
PE
Peskind E
PR
Petersen RC
PW
Poon WW
QJ
Quinn JF
RR
Rajbhandary RA
RM
Raskind M
RB
Reisberg B
RJ
Ringman JM
RE
Roberson ED
RR
Rosenberg RN
SM
Sano M
SL
Schneider LS
SW
Seeley W
SM
Shelanski ML
SM
Slifer MA
SC
Smith CD
SJ
Sonnen JA
SS
Spina S
SR
Stern RA
TR
Tanzi RE
TJ
Trojanowski JQ
TJ
Troncoso JC
VD
Van Deerlin VM
VH
Vinters HV
VJ
Vonsattel JP
WS
Weintraub S
WK
Welsh-Bohmer KA
WJ
Williamson J
WR
Woltjer RL
CL
Cantwell LB
DB
Dombroski BA
BD
Beekly D
LK
Lunetta KL
ME
Martin ER
KM
Kamboh MI
SA
Saykin AJ
RE
Reiman EM
BD
Bennett DA
MJ
Morris JC
MT
Montine TJ
GA
Goate AM
BD
Blacker D
TD
Tsuang DW
HH
Hakonarson H
KW
Kukull WA
FT
Foroud TM
HJ
Haines JL
MR
Mayeux R
PM
Pericak-Vance MA
FL
Farrer LA
SG
Schellenberg GD
Chapter II

Abstract

Summary of the research findings

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.

8,309 European ancestry cases, 7,366 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

54429
Total Participants
GWAS
Study Type
Yes
Replicated
10,523 European ancestry cases, 28,231 European ancestry controls
Replication Participants
European
Ancestry
U.S., Netherlands, Greece, Canada, Germany, U.K.
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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