Association studies of 22 candidate SNPs with late-onset Alzheimer's disease

Alzheimer's disease (AD) is a complex and multifactorial disease with the possible involvement of several genes. Complex diseases such as AD have a large affect on the public health. It was estimated in 2007 that over 5 million Americans had AD, and more than $91 billion dollars was spent by medicare on AD and other dementias. Genetics plays a significant role in the etiology of the disease, therefore, it is of public health importance that the genetics of AD be investigated. With the exception of the APOE gene as a susceptibility marker no other genes have been identified for late-onset AD (LOAD). A recent genome wide association study of 17,343 gene-based putative functional single nucleotide polymorphisms (SNPs) found 19 significant variants, including 3 linked to APOE, showing association with LOAD in several population samples. We have set out to replicate the 16 new significant associations in a large case-control cohort of American Whites. Additionally we examined six variants present in positional and/or biological candidate genes for AD. We genotyped the 22 SNPs in up to 1,009 Caucasian Americans with LOAD and up to 1,010 age matched older healthy Caucasian Americans. All variants were genotyped using 5' nuclease assays. We did not observe a statistically significant association between the SNPs with the risk of AD, either individually or stratified by APOE. Our data suggest that the association of the studied variants with LOAD, if it exists, is not statistically significant in our population study.