No Genetic Overlap Between Circulating Iron Levels and Alzheimer's Disease

J Alzheimers Dis. 2017;59(1):85-99. doi: 10.3233/JAD-170027.

Abstract

Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n∼10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n∼9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.

Keywords: Alzheimer’s disease; apolipoproteins E; dementia; ferritin; genetic profile scores; genome-wide association study; iron; population genetics; transferrin.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / genetics
  • Apolipoproteins E / genetics
  • Cohort Studies
  • Community Health Planning
  • Female
  • Ferritins / blood*
  • Genetic Association Studies / statistics & numerical data
  • Humans
  • Iron / blood*
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Transferrin / metabolism*

Substances

  • Apolipoproteins E
  • Transferrin
  • Ferritins
  • Iron