Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
In this study, we assess 34 of the most replicated genetic associations for Alzheimer's disease (AD) using data generated on Affymetrix SNP 6.0 arrays and imputed at over 5.7 million markers from a unique cohort of over 1600 neuropathologically defined AD cases and controls (1019 cases and 591 controls). Testing the top genes from the AlzGene meta-analysis, we confirm the well-known association with APOE single nucleotide polymorphisms (SNPs), the CLU, PICALM and CR1 SNPs recently implicated in unusually large data sets, and previously implicated CST3 and ACE SNPs. In the cases of CLU, PICALM and CR1, as well as in APOE, the odds ratios we find are slightly larger than those previously reported in clinical samples, consistent with what we believe to be more accurate classification of disease in the clinically characterized and neuropathologically confirmed AD cases and controls.
Neurogenomics Division, The Translational Genomics Research Institute (Gen, 445 N Fifth Street, Phoenix, AZ 85004, USA.
Jason J
JJ
Corneveaux
Amanda J
AJ
Myers
April N
AN
Allen
Jeremy J
JJ
Pruzin
Manuel
M
Ramirez
Anzhelika
A
Engel
Michael A
MA
Nalls
Kewei
K
Chen
Wendy
W
Lee
Kendria
K
Chewning
Stephen E
SE
Villa
Hunsar B
HB
Meechoovet
Jill D
JD
Gerber
Danielle
D
Frost
Hollie L
HL
Benson
Sean
S
O'Reilly
Lori B
LB
Chibnik
Joshua M
JM
Shulman
Andrew B
AB
Singleton
David W
DW
Craig
Kendall R
KR
Van Keuren-Jensen
Travis
T
Dunckley
David A
DA
Bennett
Philip L
PL
De Jager
Christopher
C
Heward
John
J
Hardy
Eric M
EM
Reiman
Matthew J
MJ
Huentelman
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D051152:Clusterin / Q000235:genetics*; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017463:Receptors, Complement 3b / Q000235:genetics*
D001057:Apolipoproteins E; C495242:CLU protein, human; C509991:CR1 protein, human; D051152:Clusterin; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; D017463:Receptors, Complement 3b