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

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Title: Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.
Authors: 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, Heutink, P
Source: Molecular Psychiatry. Dec2015, Vol. 20 Issue 12, p1588-1595. 8p.
Subjects: Genetics of Alzheimer's disease, Parkinson's disease & genetics, Single nucleotide polymorphisms, Alleles, Neurodegeneration
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. [ABSTRACT FROM AUTHOR]
Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.
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  Data: <searchLink fieldCode="AR" term="%22Desikan%2C+R+S%22">Desikan, R S</searchLink><br /><searchLink fieldCode="AR" term="%22Schork%2C+A+J%22">Schork, A J</searchLink><br /><searchLink fieldCode="AR" term="%22Wang%2C+Y%22">Wang, Y</searchLink><br /><searchLink fieldCode="AR" term="%22Witoelar%2C+A%22">Witoelar, A</searchLink><br /><searchLink fieldCode="AR" term="%22Sharma%2C+M%22">Sharma, M</searchLink><br /><searchLink fieldCode="AR" term="%22McEvoy%2C+L+K%22">McEvoy, L K</searchLink><br /><searchLink fieldCode="AR" term="%22Holland%2C+D%22">Holland, D</searchLink><br /><searchLink fieldCode="AR" term="%22Brewer%2C+J+B%22">Brewer, J B</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+C-H%22">Chen, C-H</searchLink><br /><searchLink fieldCode="AR" term="%22Thompson%2C+W+K%22">Thompson, W K</searchLink><br /><searchLink fieldCode="AR" term="%22Harold%2C+D%22">Harold, D</searchLink><br /><searchLink fieldCode="AR" term="%22Williams%2C+J%22">Williams, J</searchLink><br /><searchLink fieldCode="AR" term="%22Owen%2C+M+J%22">Owen, M J</searchLink><br /><searchLink fieldCode="AR" term="%22O'Donovan%2C+M+C%22">O'Donovan, M C</searchLink><br /><searchLink fieldCode="AR" term="%22Pericak-Vance%2C+M+A%22">Pericak-Vance, M A</searchLink><br /><searchLink fieldCode="AR" term="%22Mayeux%2C+R%22">Mayeux, R</searchLink><br /><searchLink fieldCode="AR" term="%22Haines%2C+J+L%22">Haines, J L</searchLink><br /><searchLink fieldCode="AR" term="%22Farrer%2C+L+A%22">Farrer, L A</searchLink><br /><searchLink fieldCode="AR" term="%22Schellenberg%2C+G+D%22">Schellenberg, G D</searchLink><br /><searchLink fieldCode="AR" term="%22Heutink%2C+P%22">Heutink, P</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Dec2015, Vol. 20 Issue 12, p1588-1595. 8p.
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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