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P2‐250: EXPLORING A ROLE FOR MICRORNA195 (MIR195) AS A POTENTIAL ALZHEIMER'S DISEASE BIOMARKER
Author(s) -
Cao Jiqing,
Hou Jianwei,
Zhu Li,
Zhang Larry,
El Gaamouch Farida,
Zhong Margaret B.,
Elder Gregory,
Sano Mary,
Haroutunian Vahram,
Cai Dongming
Publication year - 2019
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.2019.06.2657
Subject(s) - biomarker , microrna , dementia , clinical dementia rating , disease , alzheimer's disease , neuroscience , cerebrospinal fluid , biology , oncology , medicine , gene , genetics
DEP) to the VITamin D and OmegA-3 TriaL (VITAL; n1⁄425,871), a randomized trial of fish oil and vitaminD supplements.Wedefined 3 groups, each with n1⁄440: normal cognition; mild cognitive impairment (MCI) without NPS; MCI with NPS. Genomic DNAwas extracted from leukocytes, and DNA methylation was assayed using Illumina Infinium MethylationEPIC BeadArray technology (Methyl850K chip). DNA methylation age metrics were computed using the Horvath method; genome-wide differential methylation was examined among the 866,836CpG sites inMethylationEPIC.Annotations were performed using tools and databases in DAVID andGO (Gene Ontology). Results: A preliminary subset (n1⁄423) included persons previously selected by Diagnostic and Statistical Manualcriteria psychiatric disorder status based on structured interviews (n1⁄411 cases with current and/or past psychiatric disorder, n1⁄412 controls with no history of psychiatric disorder); we also identified those having amnestic MCI (aMCI, n1⁄411) or being cognitively normal (CN, n1⁄47) in this sub-sample. Accelerated epigenetic aging positively related to Generalized Anxiety Disorder-7 score (rho1⁄40.44; p1⁄40.04) and inversely related to 3MS cognitive score (rho1⁄4-0.44; p1⁄40.01). Comparing aMCI vs. CN, there were 103 CpG sites at p<1 x 10, but not genome-wide-significant, suggesting possible differential methylation in novel genes. GO terms for top hits included inositol phosphate-mediated signaling (INPP5A) and antigen cross-presentation (HLA-E, PSBM9, PSMC1). Several genes identified: 1) were significant hits in prior GWAS (genomewide association studies) (e.g., PSMB9, KCNMA1); 2) had multiple prior positive reports as summarized in AlzGene (e.g., POMT1); 3) were significantly enriched in AD cortical tissue expression studies (e.g., INPP5A). Additional results will be shown from the full set of n1⁄4120 participants (MCI, with and without NPS, and CN). Conclusions: Accelerated epigenetic aging was correlated with worse cognition and NPS. Non-GWA suggestions of differential methylation (gene expression) were noted in novel genes and genes previously identified as significant in AD GWAS or tissue expression studies.