期刊
MOLECULAR PSYCHIATRY
卷 20, 期 12, 页码 1588-1595出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2015.6
关键词
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资金
- National Institutes of Health [R01AG031224, K01AG029218, K02NS067427, T32 EB005970, UO1AG032984, U24-AG041689, R01 MH100351]
- Research Council of Norway [213837, 225989, 223273, 237250/EU JPND]
- South East Norway Health Authority [2013-123]
- Norwegian Health Association
- KG Jebsen Foundation
- NIH [RC2DA029475, R01HD061414]
- Robert J. Glushko and Pamela Samuelson Graduate Fellowship
- ADGC
- ADNI
- MRC [G0902227, MR/L023784/2, MR/L023784/1, MR/K013041/1] Funding Source: UKRI
- Alzheimers Research UK [ARUK-PG2014-1] Funding Source: researchfish
- Medical Research Council [MR/L023784/1, G0902227, MR/L010305/1, MR/L501517/1, MR/K013041/1, MR/L023784/2] Funding Source: researchfish
- Parkinson's UK [G-0907] Funding Source: researchfish
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 x 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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