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P1‐089: Genome scan of Alzheimer families stratified for age at onset reveals linkage to the CLU gene in 8p21.1
Author(s) -
Graff Caroline,
Sillén Anna,
Lilius Lena,
Forsell Charlotte,
Kimura Toru,
Winblad Bengt
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.637
Subject(s) - microsatellite , genetics , biology , locus (genetics) , genetic linkage , linkage disequilibrium , genetic marker , genetic association , gene , allele , single nucleotide polymorphism , genotype , haplotype
significant variants (P <0.05) one of which (rs8070723: P 1⁄4 0.012) tags the H1/H2 haplotype. The risk allele of this SNP, which tags the H1 haplotype, is associated with an increase in MAPT expression. CNV analysis identified two duplications at the APP locus in AD cases compared to none in the controls. One of these individuals has the early-onset form of Alzheimer’s disease (EOAD) while the other has early-onset dementia. While CNVs were identified at the MAPT locus, no difference was observed between cases and controls. Conclusions: Our analysis of APP, PSEN1 and PSEN2 in a LOAD GWAS dataset suggests that MAPT may have a role in causing susceptibility to LOAD through multiple variants of weak effect. In addition we replicate previous studies which observe duplications of the APP locus in early-onset AD cases.