The University of Southampton
University of Southampton Institutional Repository

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.
fb59b841-2db6-4509-850e-e761381f5861
Elbaz, Alexis
9504a106-71b2-4f12-8745-84ca0db1b487
Soto-Ortolaza, Alexandra I.
957aeb10-b061-4d60-8744-f0f76c0b01ca
Serie, Daniel J.
8dbf7734-a52a-4688-acb3-8e6e308c7c27
Aasly, Jan O.
ba34e0cc-6c06-4c25-b9fe-99e13e6b343f
Annesi, Grazia
fdc98237-0073-4486-8ea3-d39e67d30077
Auburger, Georg
f1667856-8950-41b2-9da1-2bbec6514b14
Bacon, Justin A.
80430d58-7711-455d-bbf4-a50b9acd27b4
Boczarska-Jedynak, Magdalena
f2d06fd6-2a6a-4622-9713-db32b2551d72
Bozi, Maria
9f779e34-aa59-40fd-ac0b-957252f3db1c
Brighina, Laura
8ec7a61c-1182-4a7c-ab2c-3885f9be0e1f
Chartier-Harlin, Marie-Christine
0c93b326-9215-4028-b484-baf3e0e74df8
Dardiotis, Efthimios
3a74a68b-87eb-4d35-9bcf-3c04ef26eb96
Destée, Alain
707b22e0-84b8-43f9-9f53-2092ca43bb85
Ferrarese, Carlo
a2f8c355-d6c3-49a6-b8cd-43e7b3f49474
Ferraris, Alessandro
c94dbbbc-98a9-4521-93ba-4dd68d08f8fc
Fiske, Brian
a4bb86d0-cf13-44d5-b4d6-0a0260786892
Gispert, Suzana
1bc72c80-a83e-4364-9dfa-5814775c378c
Hadjigeorgiou, Georgios M.
21ab37d2-3556-45c8-aa1e-bb10dcb4f119
Hattori, Nobutaka
9a587f54-060d-4d79-9984-c596511e7ac7
Ioannidis, John P.A.
3f25e120-eff0-47ee-a8e7-3c5c2d4d4b89
Jasinska-Myga, Barbara
fd01b5fb-74ed-48dc-b0b5-404ec5b3939c
Jeon, Beom S.
043aa969-187f-446d-8f20-6424dbb44f20
Kim, Yun Joong
d6595896-3c71-4f69-802a-f7b99f645dde
Klein, Christine
300d3d2d-55da-4c2c-84af-214134e1a424
Kruger, Rejko
2870792f-9e54-4604-8651-d47afe8937ee
Kyratzi, Elli
b5f50efd-8501-412d-96dc-ac1386ecb9bb
Lin, Chin-Hsien
ca8d9c00-d40d-4d55-82da-d93dc167c70d
Lohmann, Katja
16645a15-6d38-41dd-a511-e9238b91af3f
Loriot, Marie-Anne
7575d372-0703-4a9a-8c60-b66d90de98b3
Lynch, Timothy
fc5a3b6d-ef8c-4649-ba3f-f0d5a9fa2844
Mellick, George D.
81b03925-3ca6-4b5c-8548-9dc575b49293
Mutez, Eugénie
aaca2bb3-f675-4fac-9bee-ca9e6992b0aa
Opala, Grzegorz
68d6585a-419c-45c9-973f-0b26adccda06
Park, Sung Sup
79faf619-52d0-478c-8320-ecb506fa10ff
Petrucci, Simona
81a5fc1f-5bfd-4ca7-9070-722be9af540d
Quattrone, Aldo
0d64e33f-2a54-474b-bb28-385be83099c9
Sharma, Manu
71761491-b70d-4fa9-86fa-e64e73a61290
Silburn, Peter A.
d8e2000b-3ef5-4916-834a-bdcefb5eebec
Sohn, Young Ho
cb817946-898f-4724-a40d-098a9e9a57b4
Stefanis, Leonidas
a6f1880a-e589-4ffc-b274-dbc409f3e71d
Tadic, Vera
3e8cf18d-caa0-4312-b9f1-7c7dfb96fc30
Tomiyama, Hiroyuki
04ed7369-59de-4ea3-8d68-0d2f705076a7
Uitti, Ryan J.
aa64b8fa-0f20-4a38-a42e-96e7bb01797d
Valente, Enza Maria
33ed3b9b-6d84-4e8e-82a2-6dac7fe234ea
Vassilatis, Demetrios K.
f6061a81-30c1-43f5-a9e7-56195487823c
Vilariño-Güell, Carles
a55f2d1e-61c5-4e14-beb0-f8e9288080b4
White, Linda R.
cfbe2119-eddf-48f8-aaee-4eea65048f9e
Wirdefeldt, Karin
14cf4d55-b8bb-4990-aab5-584662347f72
Wszolek, Zbigniew K.
d1714c73-b620-4fa5-91c6-4a55ffabe3c4
Wu, Ruey-Meei
a2ea49e9-8899-4038-a727-8cef9db0a18a
Xiromerisiou, Georgia
11d4b090-d901-4f0f-904c-89d898067bc8
Maraganore, Demetrius M.
f5824832-756b-4f0f-a247-9ba64fa180c2
Farrer, Matthew J.
ac5c58ca-636a-46c7-96d0-7ef36dfe1d57
Ross, Owen A.
4df0a0d1-c79d-4465-b4cd-85396219037c
Morrison, Karen
f00890f0-2fde-4dbd-a73b-7422e1b0ede8
Heckman, Michael G.
fb59b841-2db6-4509-850e-e761381f5861
Elbaz, Alexis
9504a106-71b2-4f12-8745-84ca0db1b487
Soto-Ortolaza, Alexandra I.
957aeb10-b061-4d60-8744-f0f76c0b01ca
Serie, Daniel J.
8dbf7734-a52a-4688-acb3-8e6e308c7c27
Aasly, Jan O.
ba34e0cc-6c06-4c25-b9fe-99e13e6b343f
Annesi, Grazia
fdc98237-0073-4486-8ea3-d39e67d30077
Auburger, Georg
f1667856-8950-41b2-9da1-2bbec6514b14
Bacon, Justin A.
80430d58-7711-455d-bbf4-a50b9acd27b4
Boczarska-Jedynak, Magdalena
f2d06fd6-2a6a-4622-9713-db32b2551d72
Bozi, Maria
9f779e34-aa59-40fd-ac0b-957252f3db1c
Brighina, Laura
8ec7a61c-1182-4a7c-ab2c-3885f9be0e1f
Chartier-Harlin, Marie-Christine
0c93b326-9215-4028-b484-baf3e0e74df8
Dardiotis, Efthimios
3a74a68b-87eb-4d35-9bcf-3c04ef26eb96
Destée, Alain
707b22e0-84b8-43f9-9f53-2092ca43bb85
Ferrarese, Carlo
a2f8c355-d6c3-49a6-b8cd-43e7b3f49474
Ferraris, Alessandro
c94dbbbc-98a9-4521-93ba-4dd68d08f8fc
Fiske, Brian
a4bb86d0-cf13-44d5-b4d6-0a0260786892
Gispert, Suzana
1bc72c80-a83e-4364-9dfa-5814775c378c
Hadjigeorgiou, Georgios M.
21ab37d2-3556-45c8-aa1e-bb10dcb4f119
Hattori, Nobutaka
9a587f54-060d-4d79-9984-c596511e7ac7
Ioannidis, John P.A.
3f25e120-eff0-47ee-a8e7-3c5c2d4d4b89
Jasinska-Myga, Barbara
fd01b5fb-74ed-48dc-b0b5-404ec5b3939c
Jeon, Beom S.
043aa969-187f-446d-8f20-6424dbb44f20
Kim, Yun Joong
d6595896-3c71-4f69-802a-f7b99f645dde
Klein, Christine
300d3d2d-55da-4c2c-84af-214134e1a424
Kruger, Rejko
2870792f-9e54-4604-8651-d47afe8937ee
Kyratzi, Elli
b5f50efd-8501-412d-96dc-ac1386ecb9bb
Lin, Chin-Hsien
ca8d9c00-d40d-4d55-82da-d93dc167c70d
Lohmann, Katja
16645a15-6d38-41dd-a511-e9238b91af3f
Loriot, Marie-Anne
7575d372-0703-4a9a-8c60-b66d90de98b3
Lynch, Timothy
fc5a3b6d-ef8c-4649-ba3f-f0d5a9fa2844
Mellick, George D.
81b03925-3ca6-4b5c-8548-9dc575b49293
Mutez, Eugénie
aaca2bb3-f675-4fac-9bee-ca9e6992b0aa
Opala, Grzegorz
68d6585a-419c-45c9-973f-0b26adccda06
Park, Sung Sup
79faf619-52d0-478c-8320-ecb506fa10ff
Petrucci, Simona
81a5fc1f-5bfd-4ca7-9070-722be9af540d
Quattrone, Aldo
0d64e33f-2a54-474b-bb28-385be83099c9
Sharma, Manu
71761491-b70d-4fa9-86fa-e64e73a61290
Silburn, Peter A.
d8e2000b-3ef5-4916-834a-bdcefb5eebec
Sohn, Young Ho
cb817946-898f-4724-a40d-098a9e9a57b4
Stefanis, Leonidas
a6f1880a-e589-4ffc-b274-dbc409f3e71d
Tadic, Vera
3e8cf18d-caa0-4312-b9f1-7c7dfb96fc30
Tomiyama, Hiroyuki
04ed7369-59de-4ea3-8d68-0d2f705076a7
Uitti, Ryan J.
aa64b8fa-0f20-4a38-a42e-96e7bb01797d
Valente, Enza Maria
33ed3b9b-6d84-4e8e-82a2-6dac7fe234ea
Vassilatis, Demetrios K.
f6061a81-30c1-43f5-a9e7-56195487823c
Vilariño-Güell, Carles
a55f2d1e-61c5-4e14-beb0-f8e9288080b4
White, Linda R.
cfbe2119-eddf-48f8-aaee-4eea65048f9e
Wirdefeldt, Karin
14cf4d55-b8bb-4990-aab5-584662347f72
Wszolek, Zbigniew K.
d1714c73-b620-4fa5-91c6-4a55ffabe3c4
Wu, Ruey-Meei
a2ea49e9-8899-4038-a727-8cef9db0a18a
Xiromerisiou, Georgia
11d4b090-d901-4f0f-904c-89d898067bc8
Maraganore, Demetrius M.
f5824832-756b-4f0f-a247-9ba64fa180c2
Farrer, Matthew J.
ac5c58ca-636a-46c7-96d0-7ef36dfe1d57
Ross, Owen A.
4df0a0d1-c79d-4465-b4cd-85396219037c
Morrison, Karen
f00890f0-2fde-4dbd-a73b-7422e1b0ede8

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.

Full text not available from this repository.

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
PURE UUID: 17452a39-6672-42c9-aa25-373faee3d0e7
ORCID for Karen Morrison: ORCID iD orcid.org/0000-0003-0216-5717

Catalogue record

Date deposited: 21 Jul 2016 14:11
Last modified: 17 Dec 2019 01:32

Export record

Altmetrics

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

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×