Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/12861
Title: Genetic Variability in CLU and Its Association with Alzheimer's Disease
Authors: Guerreiro, Rita J. 
Beck, John 
Gibbs, J. Raphael 
Santana, Isabel 
Rossor, Martin N. 
Schott, Jonathan M. 
Nalls, Michael A. 
Ribeiro, Helena 
Santiago, Beatriz 
Fox, Nick C. 
Oliveira, Catarina 
Collinge, John 
Mead, Simon 
Singleton, Andrew 
Hardy, John 
Issue Date: 3-Mar-2010
Publisher: Public Library of Science
Citation: PLoS ONE. 5:3 (2010) e9510
Abstract: Recently, two large genome wide association studies in Alzheimer disease (AD) have identified variants in three different genes (CLU, PICALM and CR1) as being associated with the risk of developing AD. The strongest association was reported for an intronic single nucleotide polymorphism (SNP) in CLU. To further characterize this association we have sequenced the coding region of this gene in a total of 495 AD cases and 330 healthy controls. A total of twenty-four variants were found in both cases and controls. For the changes found in more than one individual, the genotypic frequencies were compared between cases and controls. Coding variants were found in both groups (including a nonsense mutation in a healthy subject), indicating that the pathogenicity of variants found in this gene must be carefully evaluated. We found no common coding variant associated with disease. In order to determine if common variants at the CLU locus effect expression of nearby (cis) mRNA transcripts, an expression quantitative loci (eQTL) analysis was performed. No significant eQTL associations were observed for the SNPs previously associated with AD. We conclude that common coding variability at this locus does not explain the association, and that there is no large effect of common genetic variability on expression in brain tissue. We surmise that the most likely mechanism underpinning the association is either small effects of genetic variability on resting gene expression, or effects on damage induced expression of the protein
URI: http://hdl.handle.net/10316/12861
ISSN: 1932-6203
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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