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• W2897103687 abstract "Many genome wide association studies (GWAS) of quantitative endophenotypes have been performed during various phases of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Now that the ADNI-1/GO/2 phases are complete, we performed a comprehensive updated analysis of major Alzheimer's disease (AD) phenotypes to confirm previous findings and to identify novel associations. A total of 1566 non-Hispanic Caucasian participants with GWAS and selected phenotype data from the ADNI cohort were included. Genotype data were imputed using the Haplotype Reference Consortium (HRC) reference panel after standard quality control procedures. Baseline measures of 19 phenotypes were analyzed including MRI atrophy measures (8 ROIs), FDG PET (3 ROIs), [18F]Florbetapir amyloid PET (1 meta-ROI), CSF amyloid-β 1-42 peptide (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau), as well as composite scores for memory (MEM), executive function (EF), and self- and informant- concerns regarding everyday cognition (E-Cog). Table 1 presents the full list of phenotypes and sample sizes. All phenotypes were adjusted for age and sex. MRI and cognitive measures were adjusted for education; MRI data was adjusted for intracranial volume (ICV) and magnetic field strength. Univariate GWAS analysis was performed in PLINK. The genome-wide significance threshold was set at P≤6.25x10−9 based on Bonferroni correction with the top 8 principal components of the phenotypes, which explained 85% of the total variance. 85 genome wide significant SNPs were identified across 15 of the 19 analyzed phenotypes. In 13 of those phenotypes, known the AD-associated APOE SNP (rs429358, min.P= 1.362 x10−55) was identified, with signal from the surrounding region seen in 67 SNPs near APOC1, PVRL2 and TOMM40 in the majority of phenotypes due to linkage disequilibrium effects. Outside of the APOE region, genome-wide significant results were identified in nine of the analyzed phenotypes in 17 SNPs near 13 gene regions (Table 2). Updated comprehensive GWAS of top AD associated endophenotypes identified several known and novel SNPs. The implicated genes play a role in a variety of biological functions including RNA processing, autophagy, and immune response. Genome-wide analysis of AD biomarker endophenotypes can provide insight into pathophysiological mechanisms and potential therapeutic targets for AD . List of genome wide significant SNPs, excluding 62 SNPs in APOE region, shown above with double break. Colored squares indicate genome wide significant results (-logl0(p) > 8.2) by magnitude and sign (positive or negative) of the beta value. “Nearest Gene” is closest known gene to SNP, with “Location” indicating where the SNP lies relative to the gene." @default.
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• W2897103687 date "2018-07-01" @default.
• W2897103687 modified "2023-10-16" @default.
• W2897103687 title "IC‐P‐070: GENOME‐WIDE ASSOCIATION OF TOP ALZHEIMER'S DISEASE ENDOPHENOTYPES IN ADNI DATASET" @default.
• W2897103687 doi "https://doi.org/10.1016/j.jalz.2018.06.2135" @default.
• W2897103687 hasPublicationYear "2018" @default.
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