Association of CLU and PICALM variants with Alzheimer's disease.
Two recent large genome-wide association studies have reported significant associations in the CLU (APOJ), CR1, and PICALM genes with the risk of Alzheimer's disease (AD). In order to replicate these findings, we examined 7 single nucleotide polymorphisms (SNPs) most significantly implicated by these studies in a large case-control sample comprising 2707 individuals. Principle components analysis revealed no population substructure in our sample. While no association was observed with CR1 SNPs (p = 0.30-0.457), a trend of association was seen with the PICALM (p = 0.071-0.086) and CLU (p = 0.148-0.258) SNPs. A meta-analysis of 3 studies revealed significant associations with all 3 genes. Our data from an independent and large case-control sample suggest that these gene regions should be followed up by comprehensive resequencing to find functional variants.
Kamboh
M Ilyas
MI
Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15261, United States. kamboh@pitt.edu
Minster
Ryan L
RL
Demirci
F Yesim
FY
Ganguli
Mary
M
Dekosky
Steven T
ST
Lopez
Oscar L
OL
Barmada
M Michael
MM
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D051152:Clusterin / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
C495242:CLU protein, human; D051152:Clusterin; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human