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The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants

The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants
The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants
The best validated susceptibility variants for Parkinson's disease are located in the ?-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes. Recently, a protective p.N551K-R1398H-K1423K haplotype in the leucine-rich repeat kinase 2 (LRRK2) gene was identified, with p.R1398H appearing to be the most likely functional variant. To date, the consistency of the protective effect of LRRK2 p.R1398H across MAPT and SNCA variant genotypes has not been assessed. To address this, we examined 4 SNCA variants (rs181489, rs356219, rs11931074, and rs2583988), the MAPT H1-haplotype–defining variant rs1052553, and LRRK2 p.R1398H (rs7133914) in Caucasian (n = 10,322) and Asian (n = 2289) series. There was no evidence of an interaction of LRRK2 p.R1398H with MAPT or SNCA variants (all p ? 0.10); the protective effect of p.R1398H was observed at similar magnitude across MAPT and SNCA genotypes, and the risk effects of MAPT and SNCA variants were observed consistently for LRRK2 p.R1398H genotypes. Our results indicate that the association of LRRK2 p.R1398H with Parkinson's disease is independent of SNCA and MAPT variants, and vice versa, in Caucasian and Asian populations.
266.e5-266.e14
Heckman, Michael G.
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Elbaz, Alexis
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Soto-Ortolaza, Alexandra I.
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Serie, Daniel J.
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Heckman, Michael G.
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Elbaz, Alexis
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Serie, Daniel J.
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Aasly, Jan O.
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Auburger, Georg
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Dardiotis, Efthimios
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Destée, Alain
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White, Linda R.
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Farrer, Matthew J.
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Ross, Owen A.
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Morrison, Karen
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Heckman, Michael G., Elbaz, Alexis and Soto-Ortolaza, Alexandra I. et al. (2014) The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants. Neurobiology of Aging, 35 (1), 266.e5-266.e14. (doi:10.1016/j.neurobiolaging.2013.07.013). (PMID:23962496)

Record type: Article

Abstract

The best validated susceptibility variants for Parkinson's disease are located in the ?-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes. Recently, a protective p.N551K-R1398H-K1423K haplotype in the leucine-rich repeat kinase 2 (LRRK2) gene was identified, with p.R1398H appearing to be the most likely functional variant. To date, the consistency of the protective effect of LRRK2 p.R1398H across MAPT and SNCA variant genotypes has not been assessed. To address this, we examined 4 SNCA variants (rs181489, rs356219, rs11931074, and rs2583988), the MAPT H1-haplotype–defining variant rs1052553, and LRRK2 p.R1398H (rs7133914) in Caucasian (n = 10,322) and Asian (n = 2289) series. There was no evidence of an interaction of LRRK2 p.R1398H with MAPT or SNCA variants (all p ? 0.10); the protective effect of p.R1398H was observed at similar magnitude across MAPT and SNCA genotypes, and the risk effects of MAPT and SNCA variants were observed consistently for LRRK2 p.R1398H genotypes. Our results indicate that the association of LRRK2 p.R1398H with Parkinson's disease is independent of SNCA and MAPT variants, and vice versa, in Caucasian and Asian populations.

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More information

Accepted/In Press date: 15 July 2013
Published date: January 2014
Organisations: Medical Education

Identifiers

Local EPrints ID: 398327
URI: http://eprints.soton.ac.uk/id/eprint/398327
DOI: doi:10.1016/j.neurobiolaging.2013.07.013
PURE UUID: 17452a39-6672-42c9-aa25-373faee3d0e7
ORCID for Karen Morrison: ORCID iD orcid.org/0000-0003-0216-5717

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Date deposited: 21 Jul 2016 14:11
Last modified: 15 Mar 2024 01:32

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Contributors

Author: Michael G. Heckman
Author: Alexis Elbaz
Author: Alexandra I. Soto-Ortolaza
Author: Daniel J. Serie
Author: Jan O. Aasly
Author: Grazia Annesi
Author: Georg Auburger
Author: Justin A. Bacon
Author: Magdalena Boczarska-Jedynak
Author: Maria Bozi
Author: Laura Brighina
Author: Marie-Christine Chartier-Harlin
Author: Efthimios Dardiotis
Author: Alain Destée
Author: Carlo Ferrarese
Author: Alessandro Ferraris
Author: Brian Fiske
Author: Suzana Gispert
Author: Georgios M. Hadjigeorgiou
Author: Nobutaka Hattori
Author: John P.A. Ioannidis
Author: Barbara Jasinska-Myga
Author: Beom S. Jeon
Author: Yun Joong Kim
Author: Christine Klein
Author: Rejko Kruger
Author: Elli Kyratzi
Author: Chin-Hsien Lin
Author: Katja Lohmann
Author: Marie-Anne Loriot
Author: Timothy Lynch
Author: George D. Mellick
Author: Eugénie Mutez
Author: Grzegorz Opala
Author: Sung Sup Park
Author: Simona Petrucci
Author: Aldo Quattrone
Author: Manu Sharma
Author: Peter A. Silburn
Author: Young Ho Sohn
Author: Leonidas Stefanis
Author: Vera Tadic
Author: Hiroyuki Tomiyama
Author: Ryan J. Uitti
Author: Enza Maria Valente
Author: Demetrios K. Vassilatis
Author: Carles Vilariño-Güell
Author: Linda R. White
Author: Karin Wirdefeldt
Author: Zbigniew K. Wszolek
Author: Ruey-Meei Wu
Author: Georgia Xiromerisiou
Author: Demetrius M. Maraganore
Author: Matthew J. Farrer
Author: Owen A. Ross
Author: Karen Morrison ORCID iD

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