- 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.
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.