Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.
The gene encoding apolipoprotein E (APOE) on chromosome 19 is the only confirmed susceptibility locus for late-onset Alzheimer's disease. To identify other risk loci, we conducted a large genome-wide association study of 2,032 individuals from France with Alzheimer's disease (cases) and 5,328 controls. Markers outside APOE with suggestive evidence of association (P < 10(-5)) were examined in collections from Belgium, Finland, Italy and Spain totaling 3,978 Alzheimer's disease cases and 3,297 controls. Two loci gave replicated evidence of association: one within CLU (also called APOJ), encoding clusterin or apolipoprotein J, on chromosome 8 (rs11136000, OR = 0.86, 95% CI 0.81-0.90, P = 7.5 x 10(-9) for combined data) and the other within CR1, encoding the complement component (3b/4b) receptor 1, on chromosome 1 (rs6656401, OR = 1.21, 95% CI 1.14-1.29, P = 3.7 x 10(-9) for combined data). Previous biological studies support roles of CLU and CR1 in the clearance of beta amyloid (Abeta) peptide, the principal constituent of amyloid plaques, which are one of the major brain lesions of individuals with Alzheimer's disease.
Lambert
Jean-Charles
JC
Inserm U744, Lille, France.
Heath
Simon
S
Even
Gael
G
Campion
Dominique
D
Sleegers
Kristel
K
Hiltunen
Mikko
M
Combarros
Onofre
O
Zelenika
Diana
D
Bullido
Maria J
MJ
Tavernier
Béatrice
B
Letenneur
Luc
L
Bettens
Karolien
K
Berr
Claudine
C
Pasquier
Florence
F
Fiévet
Nathalie
N
Barberger-Gateau
Pascale
P
Engelborghs
Sebastiaan
S
De Deyn
Peter
P
Mateo
Ignacio
I
Franck
Ana
A
Helisalmi
Seppo
S
Porcellini
Elisa
E
Hanon
Olivier
O
de Pancorbo
Marian M
MM
Lendon
Corinne
C
Dufouil
Carole
C
Jaillard
Céline
C
Leveillard
Thierry
T
Alvarez
Victoria
V
Bosco
Paolo
P
Mancuso
Michelangelo
M
Panza
Francesco
F
Nacmias
Benedetta
B
Bossù
Paola
P
Piccardi
Paola
P
Annoni
Giorgio
G
Seripa
Davide
D
Galimberti
Daniela
D
Hannequin
Didier
D
Licastro
Federico
F
Soininen
Hilkka
H
Ritchie
Karen
K
Blanché
Hélène
H
Dartigues
Jean-François
JF
Tzourio
Christophe
C
Gut
Ivo
I
Van Broeckhoven
Christine
C
Alpérovitch
Annick
A
Lathrop
Mark
M
Amouyel
Philippe
P
D000544:Alzheimer Disease / Q000235:genetics*; D051152:Clusterin / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017463:Receptors, Complement 3b / Q000235:genetics*; D044465:White People / Q000235:genetics
C495242:CLU protein, human; C509991:CR1 protein, human; D051152:Clusterin; D017463:Receptors, Complement 3b