3 years ago

Plasma apolipoprotein E levels and risk of dementia—A Mendelian randomization study of 106,562 individuals

In recent prospective studies, low plasma levels of apolipoprotein E (apoE) are associated with high risk of dementia. Whether this reflects a causal association remains to be established. Methods Using a Mendelian randomization approach, we studied 106,562 and 75,260 individuals from the general population in observational and genetic analyses, respectively. Results In observational analyses risk of Alzheimer disease and all dementia increased stepwise as a function of stepwise lower apoE levels (P for trend, 2 × 10−17 and 9 × 10−21). APOE-weighted allele scores were associated with stepwise decreases in apoE (P for trend, <1 × 10−300). In instrumental variable analysis, the causal risk ratios for a 1 mg/dL genetically determined lower apoE were 1.41 (1.27–1.57) for Alzheimer disease and 1.33 (1.25–1.43) for all dementia (F-statistics = 3821). Discussion Genetic and hence lifelong low apoE is associated with high risk of dementia in the general population. The concordance between observational and genetic estimates suggests a potential causal relationship.

Publisher URL: www.sciencedirect.com/science

DOI: S1552526017302364

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.