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.