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

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.

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Acknowledgements

We would like to thank Drs. Irene Litvan, Subhojit Roy and Marilyn Albert for helpful comments on an earlier version of this manuscript. This research was supported by grants from the National Institutes of Health (R01AG031224, K01AG029218, K02NS067427, T32 EB005970, UO1AG032984, U24-AG041689, and R01 MH100351), the Research Council of Norway (#213837, #225989, #223273, #237250/EU JPND), the South East Norway Health Authority (2013-123), the Norwegian Health Association and the KG Jebsen Foundation. AJS was supported by NIH grants RC2DA029475 and R01HD061414 and the Robert J. Glushko and Pamela Samuelson Graduate Fellowship. Please see Supplementary Acknowledgements for ADGC and ADNI funding sources.

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Correspondence to R S Desikan or O A Andreassen or A M Dale.

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Competing interests

Disclosures Dr. Anders M. Dale is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is also a member of the Scientific Advisory Board of Human Longevity, Inc. (HLI), and receives funding through research agreements with General Electric Healthcare (GEHC) and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. Dr. Linda K. McEvoy has stock options in CorTechs Labs, Inc. Dr. James B. Brewer holds stock options in CorTechs Labs, Inc and serves on the advisory board and receives financial support from the Eli Lilly Biomarker Unit (Amyvid). Dr. Brewer also receives research support from General Electric and Janssen Alzheimer Immunotherapy.

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