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

  • Author(s): Desikan, RS
  • Schork, AJ
  • Wang, Y
  • Witoelar, A
  • Sharma, M
  • McEvoy, LK
  • Holland, D
  • Brewer, JB
  • Chen, CH
  • Thompson, WK
  • Harold, D
  • Williams, J
  • Owen, MJ
  • O'Donovan, MC
  • Pericak-Vance, MA
  • Mayeux, R
  • Haines, JL
  • Farrer, LA
  • Schellenberg, GD
  • Heutink, P
  • Singleton, AB
  • Brice, A
  • Wood, NW
  • Hardy, J
  • Martinez, M
  • Choi, SH
  • Destefano, A
  • Ikram, MA
  • Bis, JC
  • Smith, A
  • Fitzpatrick, AL
  • Launer, L
  • Van Duijn, C
  • Seshadri, S
  • Ulstein, ID
  • Aarsland, D
  • Fladby, T
  • Djurovic, S
  • Hyman, BT
  • Snaedal, J
  • Stefansson, H
  • Stefansson, K
  • Gasser, T
  • Andreassen, OA
  • Dale, AM
  • et al.

Published Web Location

https://doi.org/10.1038/mp.2015.6
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.

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