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O3‐01‐02: Genetic predictors of progression of cognitive impairment in Two large Canadian cohorts: CSHA and ACCORD
Author(s) -
Hsiung GingYuek,
Greenwood Talitha,
Fok Alice,
Chen Cindy,
Sadovnick Dessa
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.2011.05.2387
Subject(s) - dementia , cohort , medicine , cognitive decline , longitudinal study , logistic regression , cohort study , odds ratio , population , gerontology , cognition , demography , disease , psychiatry , pathology , environmental health , sociology
study-specific findings in a fixed-effects meta-analysis of 9,232 participants. Results: We identified 46 SNPs at six loci whose p-values for association with HV surpassed our genome-wide significance threshold corresponding to one expected false positive (p < 4.0~ A—10 ). Our findings included three independent chromosome 12 loci: 25 SNPs within or near WIF1 (p1⁄42.2~ A—10 ), 5 SNPs within MSRB3 (p1⁄45.5~ A—10 ), and 6 SNPs within or near FBXW8 (p1⁄43.7~ A—10 ). The remaining associations included: 1 SNP on chromosome 2 within DPP (p1⁄45.2~ A—10 ) and 9 SNPs on chromosome 9 within ASTN2 (p1⁄41.0~ A—10 ). Conclusions: Our community-based genome-wide association meta-analysis identified several new associations with hippocampal volume. These associations implicate genes related to embryonic development (WIF1), oxidative stress via methionine reduction (MSR3B), ubiquitinylation of toxic proteins (FBXW8), proline cleaving enzymes targeted by new diabetes medications (DPP), and neuronal migration (ASTN2) indicating potential new targets that may influence hippocampal size and therefore possibly dementia risk through regulation of novel biological pathways.