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

We investigated genetic overlap between Alzheimer’s disease (AD) and Parkinson’s disease (PD). Using summary statistics (p-values) from large recent genomewide association studies (GWAS) (total n = 89,904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with bot...

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Detalles Bibliográficos
Autores principales: Desikan, Rahul S., Schork, Andrew J., Wang, Yunpeng, Witoelar, Aree, Sharma, Manu, McEvoy, Linda K., Holland, Dominic, Brewer, James B., Chen, Chi-Hua, Thompson, Wesley K., Harold, Denise, Williams, Julie, Owen, Michael J., O’Donovan, Michael C., Pericak-Vance, Margaret A., Mayeux, Richard, Haines, Jonathan L., Farrer, Lindsay A., Schellenberg, Gerard D., Heutink, Peter, Singleton, Andrew B., Brice, Alexis, Wood, Nicolas W., Hardy, John, Martinez, Maria, Choi, Seung Hoi, DeStefano, Anita, Ikram, M. Arfan, Bis, Joshua C., Smith, Albert, Fitzpatrick, Annette L., Launer, Lenore, van Duijn, Cornelia, Seshadri, Sudha, Ulstein, Ingun Dina, Aarsland, Dag, Fladby, Tormod, Djurovic, Srdjan, Hyman, Bradley T., Snaedal, Jon, Stefansson, Hreinn, Stefansson, Kari, Gasser, Thomas, Andreassen, Ole A., Dale, Anders M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539304/
https://www.ncbi.nlm.nih.gov/pubmed/25687773
http://dx.doi.org/10.1038/mp.2015.6
Descripción
Sumario:We investigated genetic overlap between Alzheimer’s disease (AD) and Parkinson’s disease (PD). Using summary statistics (p-values) from large recent genomewide 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 5 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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