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

R. S. Desikan; A. J. Schork; Y. Wang; A. Witoelar; M. Sharma; L. K. McEvoy; D. Holland; J. B. Brewer; C. H. Chen; W. K. Thompson; D. Harold; J. Williams; M. J. Owen; M. C. O'Donovan; M. A. Pericak-Vance; R. Mayeux; J. L. Haines; L. A. Farrer; G. D. Schellenberg; P. Heutink; A. B. Singleton; A. Brice; N. W. Wood; J. Hardy; M. Martinez; S. H. Choi; A. Destefano; M. A. Ikram; J. C. Bis; A. Smith; A. L. Fitzpatrick; L. Launer; C. Van Duijn; S. Seshadri; I. D. Ulstein; D. Aarsland; T. Fladby; S. Djurovic; B. T. Hyman; J. Snaedal; H. Stefansson; K. Stefansson; T. Gasser; O. A. Andreassen; A. M. Dale

doi:10.1038/mp.2015.6

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

R. S. Desikan, A. J. Schork, Y. Wang, A. Witoelar, M. Sharma, L. K. McEvoy, D. Holland, J. B. Brewer, C. H. Chen, W. K. Thompson, D. Harold, J. Williams, M. J. Owen, M. C. O'Donovan, M. A. Pericak-Vance, R. Mayeux, J. L. Haines, L. A. Farrer, G. D. Schellenberg, P. HeutinkA. B. Singleton, A. Brice, N. W. Wood, J. Hardy, M. Martinez, S. H. Choi, A. Destefano, M. A. Ikram, J. C. Bis, A. Smith, A. L. Fitzpatrick, L. Launer, C. Van Duijn, S. Seshadri, I. D. Ulstein, D. Aarsland, T. Fladby, S. Djurovic, B. T. Hyman, J. Snaedal, H. Stefansson, K. Stefansson, T. Gasser, O. A. Andreassen, A. M. Dale

Biggs Alzheimer's Institute

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1588-1595
Number of pages	8
Journal	Molecular psychiatry
Volume	20
Issue number	12
DOIs	https://doi.org/10.1038/mp.2015.6
State	Published - Dec 1 2015

ASJC Scopus subject areas

Molecular Biology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

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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., ... Dale, A. M. (2015). Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. Molecular psychiatry, 20(12), 1588-1595. https://doi.org/10.1038/mp.2015.6

Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. / 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.; Singleton, A. B.; Brice, A.; Wood, N. W.; Hardy, J.; Martinez, M.; Choi, S. H.; Destefano, A.; Ikram, M. A.; Bis, J. C.; Smith, A.; Fitzpatrick, A. L.; Launer, L.; Van Duijn, C.; Seshadri, S.; Ulstein, I. D.; Aarsland, D.; Fladby, T.; Djurovic, S.; Hyman, B. T.; Snaedal, J.; Stefansson, H.; Stefansson, K.; Gasser, T.; Andreassen, O. A.; Dale, A. M.

In: Molecular psychiatry, Vol. 20, No. 12, 01.12.2015, p. 1588-1595.

Research output: Contribution to journal › Article › peer-review

Desikan, RS, Schork, AJ, Wang, Y, Witoelar, A, Sharma, M, McEvoy, LK, Holland, D, Brewer, JB, Chen, CH, Thompson, WK, Harold, D, Williams, J, Owen, MJ, O'Donovan, MC, Pericak-Vance, MA, Mayeux, R, Haines, JL, Farrer, LA, Schellenberg, GD, Heutink, P, Singleton, AB, Brice, A, Wood, NW, Hardy, J, Martinez, M, Choi, SH, Destefano, A, Ikram, MA, Bis, JC, Smith, A, Fitzpatrick, AL, Launer, L, Van Duijn, C, Seshadri, S, Ulstein, ID, Aarsland, D, Fladby, T, Djurovic, S, Hyman, BT, Snaedal, J, Stefansson, H, Stefansson, K, Gasser, T, Andreassen, OA & Dale, AM 2015, 'Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus', Molecular psychiatry, vol. 20, no. 12, pp. 1588-1595. https://doi.org/10.1038/mp.2015.6

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. ; Singleton, A. B. ; Brice, A. ; Wood, N. W. ; Hardy, J. ; Martinez, M. ; Choi, S. H. ; Destefano, A. ; Ikram, M. A. ; Bis, J. C. ; Smith, A. ; Fitzpatrick, A. L. ; Launer, L. ; Van Duijn, C. ; Seshadri, S. ; Ulstein, I. D. ; Aarsland, D. ; Fladby, T. ; Djurovic, S. ; Hyman, B. T. ; Snaedal, J. ; Stefansson, H. ; Stefansson, K. ; Gasser, T. ; Andreassen, O. A. ; Dale, A. M. / Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. In: Molecular psychiatry. 2015 ; Vol. 20, No. 12. pp. 1588-1595.

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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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AU - Schork, A. J.

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AU - Sharma, M.

AU - McEvoy, L. K.

AU - Holland, D.

AU - Brewer, J. B.

AU - Chen, C. H.

AU - Thompson, W. K.

AU - Harold, D.

AU - Williams, J.

AU - Owen, M. J.

AU - O'Donovan, M. C.

AU - Pericak-Vance, M. A.

AU - Mayeux, R.

AU - Haines, J. L.

AU - Farrer, L. A.

AU - Schellenberg, G. D.

AU - Heutink, P.

AU - Singleton, A. B.

AU - Brice, A.

AU - Wood, N. W.

AU - Hardy, J.

AU - Martinez, M.

AU - Choi, S. H.

AU - Destefano, A.

AU - Ikram, M. A.

AU - Bis, J. C.

AU - Smith, A.

AU - Fitzpatrick, A. L.

AU - Launer, L.

AU - Van Duijn, C.

AU - Seshadri, S.

AU - Ulstein, I. D.

AU - Aarsland, D.

AU - Fladby, T.

AU - Djurovic, S.

AU - Hyman, B. T.

AU - Snaedal, J.

AU - Stefansson, H.

AU - Stefansson, K.

AU - Gasser, T.

AU - Andreassen, O. A.

AU - Dale, A. M.

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