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Associations of the Top 20 Alzheimer Disease Risk Variants With Brain Amyloidosis.


ABSTRACT: Importance:Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide association studies have identified more than 20 AD risk genes. The precise mechanism through which many of these genes are associated with AD remains unknown. Objective:To investigate the association of the top 20 AD risk variants with brain amyloidosis. Design, Setting, and Participants:This study analyzed the genetic and florbetapir F 18 data from 322 cognitively normal control individuals, 496 individuals with mild cognitive impairment, and 159 individuals with AD dementia who had genome-wide association studies and 18F-florbetapir positron emission tomographic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective, observational, multisite tertiary center clinical and biomarker study. This ongoing study began in 2005. Main Outcomes and Measures:The study tested the association of AD risk allele carrier status (exposure) with florbetapir mean standard uptake value ratio (outcome) using stepwise multivariable linear regression while controlling for age, sex, and apolipoprotein E ?4 genotype. The study also reports on an exploratory 3-dimensional stepwise regression model using an unbiased voxelwise approach in Statistical Parametric Mapping 8 with cluster and significance thresholds at 50 voxels and uncorrected P?

SUBMITTER: Apostolova LG 

PROVIDER: S-EPMC5885860 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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<h4>Importance</h4>Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide association studies have identified more than 20 AD risk genes. The precise mechanism through which many of these genes are associated with AD remains unknown.<h4>Objective</h4>To investigate the association of the top 20 AD risk variants with brain amyloidosis.<h4>Design, setting, and participants</h4>This study analyzed the genetic and florbetapir F 18 data from 322 cognitively normal control individuals, 496  ...[more]

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