Genome wide association study of gene expression levels in Alzheimer's disease

Project: Research project

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DESCRIPTION (provided by applicant): Late-onset Alzheimer's disease (LOAD) has a substantial genetic component estimated to be as high as 80%, much of which remains unexplained. Genome-wide association studies (GWAS) are emerging as a powerful approach in deciphering the genetic risk factors for common-complex diseases. It has been proposed that the genetic basis of common-complex diseases is mainly due to regulatory factors. There have been several GWAS in humans utilizing messenger RNA (mRNA) expression levels from lymphoblasts and one using cortical tissue from human brains. These studies identified many cis-SNPs that show strong association with transcript levels. Many of these associations achieved genome wide significance when only hundreds of samples are analyzed. We have recently analyzed 313,504 single-nucleotide polymorphisms (SNPs) using the Illumina platform in 2,099 subjects from LOAD case-control series. Of these subjects, there are 200 pathologically confirmed AD cases and 197 non-AD subjects with cerebellar RNA samples. In our preliminary analysis of mRNA expression levels for 12 LOAD candidate genes from cerebella of
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