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Late-onset Alzheimer's disease (LOAD) is a genetically complex neurodegenerative disorder. Currently, only the epsilon4 allele of the Apolipoprotein E gene has been identified unequivocally as a genetic susceptibility factor for LOAD. Others remain to be found. In 2002 we observed genome-wide significant evidence of linkage to a region on chromosome 10q11.23-q21.3 [Myers et al. (2002) Am J Med Genet 114:235-244]. Our objective in this study was to test every gene within the maximum LOD-1 linkage region, for association with LOAD. We obtained results for 528 SNPs from 67 genes, with an average density of 1 SNP every 10 kb within the genes. We demonstrated nominally significant association with LOAD for 4 SNPs: rs1881747 near DKK1 (P = 0.011, OR = 1.24), rs2279420 in ANK3 (P = 0.022, OR = 0.79), rs2306402 in CTNNA3 (P = 0.024, OR = 1.18), and rs5030882 in CXXC6 (P = 0.046, OR = 1.29) in 1,160 cases and 1,389 controls. These results would not survive correction for multiple testing but warrant attempts at confirmation in independent samples.

Original publication

DOI

10.1002/ajmg.b.30670

Type

Journal article

Journal

Am J Med Genet B Neuropsychiatr Genet

Publication Date

05/09/2008

Volume

147B

Pages

727 - 731

Keywords

Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Ankyrins, Case-Control Studies, Chromosomes, Human, Pair 10, DNA Mutational Analysis, DNA-Binding Proteins, Female, Genetic Linkage, Genetic Predisposition to Disease, Genotype, Humans, Intercellular Signaling Peptides and Proteins, Male, Middle Aged, Mixed Function Oxygenases, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins, alpha Catenin