Replication of CLU, CR1, and PICALM associations with alzheimer disease.
OBJECTIVE
To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease.


METHODS
Follow-up case-control association study.


METHODS
The Mayo Clinics at Jacksonville, Florida, and Rochester, Minnesota.


METHODS
Community-based patients of European descent with late-onset Alzheimer disease (LOAD) and controls without dementia who were seen at the Mayo clinics, and autopsy-confirmed cases and controls whose pathology was evaluated at the Mayo Clinic in Jacksonville. Additional samples were obtained from the National Cell Repository for Alzheimer Disease (NCRAD). A total of 1829 LOAD cases and 2576 controls were analyzed.


METHODS
The most significant single-nucleotide polymorphisms in CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179) were tested for allelic association with LOAD. Main Outcome Measure Clinical or pathology-confirmed diagnosis of LOAD.


RESULTS
Odds ratios for CLU, CR1, and PICALM were 0.82, 1.15, and 0.80, respectively, comparable in direction and magnitude with those originally reported. P values were 8.6 x 10(-5), .014, and 1.3 x 10(-5), respectively; they remain significant even after Bonferroni correction for the 3 single-nucleotide polymorphisms tested.


CONCLUSIONS
These results show near-perfect replication and provide the first additional evidence that CLU, CR1, and PICALM are associated with the risk of LOAD.
Carrasquillo
Minerva M
MM
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd, Birdsall Building, Jacksonville, FL 32224, USA.
Belbin
Olivia
O
Hunter
Talisha A
TA
Ma
Li
L
Bisceglio
Gina D
GD
Zou
Fanggeng
F
Crook
Julia E
JE
Pankratz
V Shane
VS
Dickson
Dennis W
DW
Graff-Radford
Neill R
NR
Petersen
Ronald C
RC
Morgan
Kevin
K
Younkin
Steven G
SG
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D051152:Clusterin / Q000235:genetics*; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017463:Receptors, Complement 3b / Q000235:genetics*; D012111:Residence Characteristics; D044465:White People
C495242:CLU protein, human; C509991:CR1 protein, human; D051152:Clusterin; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; D017463:Receptors, Complement 3b