APOE and dementia - resequencing and genotyping in 105,597 individuals.

ABSTRACT:

Introduction

The mechanism behind the strong association between the ɛ2/ɛ3/ɛ4 apolipoprotein E gene (APOE) polymorphism and Alzheimer's disease is not well-characterized. Because low plasma levels of apoE associate with risk of dementia, genetic variants altering apoE levels in general may also associate with dementia.

Methods

The APOE gene was sequenced in 10,369 individuals, and nine amino acid-changing variants with frequencies ≥2/10,000 were further genotyped in 95,228 individuals. Plasma apoE levels were measured directly.

Results

Risk of all dementia and Alzheimer's disease (AD) increased with decreasing genetically determined apoE levels (P = 5 × 10^-4 and P = 1 × 10^-4 after APOE ɛ2/ɛ3/ɛ4 adjustment). Hazard ratios (95% confidence intervals

SUBMITTER: Rasmussen KL 

PROVIDER: S-EPMC7984319 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature