Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus

Mol Psychiatry. 2015 Dec;20(12):1588-95. doi: 10.1038/mp.2015.6. Epub 2015 Feb 17.

Abstract

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / genetics*
  • Apolipoproteins E / genetics
  • Brain / pathology
  • Chromosomes, Human, Pair 17
  • Female
  • Genetic Loci
  • Genetic Pleiotropy
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide
  • tau Proteins / genetics*

Substances

  • Apolipoproteins E
  • MAPT protein, human
  • tau Proteins

Grant support