학술논문
Genetic overlap between Alzheimer’s disease and Parkinson’s disease at the MAPT locus
Document Type
article
Author
Desikan, RS; Schork, AJ; Wang, Y; Witoelar, A; Sharma, M; McEvoy, LK; Holland, D; Brewer, JB; Chen, C-H; 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
Source
Molecular Psychiatry. 20(12)
Subject
Language
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.