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P1‐278: Results from dense SNP genotyping of the 9q22‐q31 CRI in the NIMH and NCRAD AD cohorts
Author(s) -
Perry Rodney,
Wiener Howard,
Go Rodney
Publication year - 2011
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.2011.05.559
Subject(s) - single nucleotide polymorphism , genotyping , snp , international hapmap project , snp genotyping , candidate gene , genetics , biology , genotype , gene
Background: Linkage scans of Alzheimer’s disease (AD) families have identified the 9q22 region as a candidate region of interest (CRI). Second to APOE, the 9q22 signal was the most suggestive from the linkage scan of the NIMH Alzheimer’s Disease Genetic Initiative (ADGI). Additional microsatellite markers, narrowed the 1 LOD region to 11.5 cm (91.5-103 Mb). Four candidate genes located between 2-6 Mb proximal to this peak have been found significantly associated with AD.Methods: To determine more precisely the location of these signals, dense SNP genotyping of the 9q21-9q31 region, covering a total ofw18 Mb which includes this region and the proximal 6 Mb was performed. Haplotag SNPs and unblocked SNPs were chosen from HapMap. SNPs in reported CNVs from this region, and SNPs covering four genes CRI, CLU, PICALM, and TOMM40 were also genotyped, resulting in a total ofw 5800 SNPs. Genotyping used the Illumina iSelect platform. Results: Dense SNP genotyping was performed in the NIMH and NCRAD cohorts. Using Family Based Association Testing, besides confirming the APOE/TOMM40 and NTRK2 associations, the strongest and most consistent signals for additive and dominant models were at 86.6 Mb, 91.3 Mb, 93.2 Mb, 96.25 Mb, 97.8 Mb, 100.3 Mb, and 102.5 Mb. Conclusions: HIATL1, HABP4, GABBR2, and PRG-3, are genes in these key regions known to be expressed in brain and involved in synaptic transmission and neuroplasticity. In depth analyses including possible CNVs, and results from deep sequencing of these genes and others to identify causal variants will be presented.