作者
Rahul S Desikan, Andrew J Schork, Yunpeng Wang, Aree Witoelar, Manu Sharma, Linda K McEvoy, Dominic Holland, James B Brewer, Chi-Hua Chen, Wesley K Thompson, Denise Harold, Julie Williams, Michael J Owen, Michael C O'Donovan, Margaret A Pericak-Vance, Richard Mayeux, Jonathan L Haines, Lindsay A Farrer, Gerard D Schellenberg, Peter Heutink, Andrew B Singleton, Alexis Brice, Nicolas W Wood, John Hardy, Maria Martinez, Seung Hoi Choi, Anita DeStefano, M Arfan Ikram, Joshua C Bis, Albert Smith, Annette L Fitzpatrick, Lenore Launer, Cornelia van Duijn, Sudha Seshadri, Ingun Dina Ulstein, Dag Aarsland, Tormod Fladby, Srdjan Djurovic, Bradley T Hyman, Jon Snaedal, Hreinn Stefansson, Kari Stefansson, Thomas Gasser, Ole A Andreassen, Anders M Dale
发表日期
2015/12
期刊
Molecular psychiatry
卷号
20
期号
12
页码范围
1588-1595
出版商
Nature Publishing Group
简介
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 …
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RS Desikan, AJ Schork, Y Wang, A Witoelar, M Sharma… - Molecular psychiatry, 2015