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.
Corneveaux
Jason J
JJ
Neurogenomics Division, The Translational Genomics Research Institute (Gen, 445 N Fifth Street, Phoenix, AZ 85004, USA.
Myers
Amanda J
AJ
Allen
April N
AN
Pruzin
Jeremy J
JJ
Ramirez
Manuel
M
Engel
Anzhelika
A
Nalls
Michael A
MA
Chen
Kewei
K
Lee
Wendy
W
Chewning
Kendria
K
Villa
Stephen E
SE
Meechoovet
Hunsar B
HB
Gerber
Jill D
JD
Frost
Danielle
D
Benson
Hollie L
HL
O'Reilly
Sean
S
Chibnik
Lori B
LB
Shulman
Joshua M
JM
Singleton
Andrew B
AB
Craig
David W
DW
Van Keuren-Jensen
Kendall R
KR
Dunckley
Travis
T
Bennett
David A
DA
De Jager
Philip L
PL
Heward
Christopher
C
Hardy
John
J
Reiman
Eric M
EM
Huentelman
Matthew J
MJ
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