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P1‐057: SEARCH FOR RECESSIVE ALZHEIMER DISEASE LOCI IN AFRICAN AMERICANS BY GENOME‐WIDE STUDY OF RUNS OF HOMOZYGOSITY
Author(s) -
Rogaeva Ekaterina,
Ghani Mahdi,
Reitz Christiane,
Lee Joseph H.,
Vardarajan Badri N.,
Tosto Giuseppe,
St. GeorgeHyslop Peter,
Mayeux Richard
Publication year - 2014
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.2014.05.293
Subject(s) - genome wide association study , runs of homozygosity , genetics , snp , biology , snp array , single nucleotide polymorphism , candidate gene , genetic association , haplotype , genotype , gene
samples or directly from available brain tissues (from the Douglas Bell Canada Brain Bank). For a subset of post-mortem samples, the density of senile plaques (SP) and neurofibrillary tangles (NFT) were evaluated by a neuropathologist. Single nucleotide polymorphisms (SNPs) significantly associated with the disease, the age of onset or with neuropathological data will be assessed for replication in the population from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Results: With the standard casecontrol analysis, only four SNPs reached genome-wide significance (p< 5 x 10 -8). These four SNPs (rs429358, rs2075650, rs405509 and rs8106922) were all located on chromosome 19 near APOE gene. The strongest SNP (rs429358, p1⁄4 4.1 x 10 -24) also correlated with the age of onset (p1⁄4 2.4 x 10 -4), the density of SP in the frontal cortex (p1⁄4 6.5 x 10 -8) and in the CA1 region of the hippocampus (p1⁄4 3.6 x 10 -3), and the density of NFT in the frontal cortex (p1⁄4 7.3 x 10 -7) and in the CA1 region of the hippocampus (p1⁄4 4.6 x 10 -3). A second analysis is currently being performed in an effort to find other SNPs that correlate with pathology-related biomarkers. SNPs will be selected based on P values and the number of significant correlations with different biomarkers from our study and the ADNI database. Conclusions: The contribution of APOE to late-onset Alzheimer’s disease has already been well established. The present study will help to identify genes never before associated with the disease.