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

R. S. Desikan, A. J. Schork, Y. Wang, A. Witoelar, M. Sharma, L. K. McEvoy, D. Holland, J. B. Brewer, C. H. Chen, W. K. Thompson, D. Harold, J. Williams, M. J. Owen, M. C. O'Donovan, M. A. Pericak-Vance, R. Mayeux, J. L. Haines, L. A. Farrer, G. D. Schellenberg, P. HeutinkA. B. Singleton, A. Brice, N. W. Wood, J. Hardy, M. Martinez, S. H. Choi, A. Destefano, M. A. Ikram, J. C. Bis, A. Smith, A. L. Fitzpatrick, L. Launer, C. Van Duijn, S. Seshadri, I. D. Ulstein, D. Aarsland, T. Fladby, S. Djurovic, B. T. Hyman, J. Snaedal, H. Stefansson, K. Stefansson, T. Gasser, O. A. Andreassen, A. M. Dale

Research output: Contribution to journalArticle

71 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1588-1595
Number of pages8
JournalMolecular psychiatry
Volume20
Issue number12
DOIs
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Desikan, R. S., Schork, A. J., Wang, Y., Witoelar, A., Sharma, M., McEvoy, L. K., Holland, D., Brewer, J. B., Chen, C. H., Thompson, W. K., Harold, D., Williams, J., Owen, M. J., O'Donovan, M. C., Pericak-Vance, M. A., Mayeux, R., Haines, J. L., Farrer, L. A., Schellenberg, G. D., ... Dale, A. M. (2015). Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. Molecular psychiatry, 20(12), 1588-1595. https://doi.org/10.1038/mp.2015.6