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

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

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Author Heckman, Michael G.
Elbaz, Alexis
Soto-Ortolaza, Alexandra I.
Serie, Daniel J.
Aasly, Jan O.
Annesi, Grazia
Auburger, Georg
Bacon, Justin A.
Boczarska-Jedynak, Magdalena
Bozi, Maria
Brighina, Laura
Chartier-Harlin, Marie-Christine
Dardiotis, Efthimios
Destee, Alain
Ferrarese, Carlo
Ferraris, Alessandro
Fiske, Brian
Gispert, Suzana
Hadjigeorgiou, Georgios M.
Hattori, Nobutaka
Ioannidis, John P. A.
Jasinska-Myga, Barbara
Jeon, Beom S.
Kim, Yun Joong
Klein, Christine
Kruger, Rejko
Kyratzi, Elli
Lin, Chin-Hsien
Lohmann, Katja
Loriot, Marie-Anne
Lynch, Timothy
Mellick, George D.
Mutez, Eugenie
Opala, Grzegorz
Park, Sung Sup
Petrucci, Simona
Quattrone, Aldo
Sharma, Manu
Silburn, Peter A.
Sohn, Young Ho
Stefanis, Leonidas
Tadic, Vera
Tomiyama, Hiroyuki
Uitti, Ryan J.
Valente, Enza Maria
Vassilatis, Demetrios K.
Vilarino-Guell, Carles
White, Linda R.
Wirdefeldt, Karin
Wszolek, Zbigniew K.
Wu, Ruey-Meei
Xiromerisiou, Georgia
Maraganore, Demetrius M.
Farrer, Matthew J.
Ross, Owen A.
on behalf of the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium
Title The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants
Formatted title
The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants
Journal name Neurobiology of Aging   Check publisher's open access policy
ISSN 0197-4580
1558-1497
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.neurobiolaging.2013.07.013
Open Access Status DOI
Volume 35
Issue 1
Start page 266.e5
End page 266.e14
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Subject 2800 Neuroscience
1302 Ageing
2728 Clinical Neurology
1309 Developmental Biology
2717 Geriatrics and Gerontology
Abstract The best validated susceptibility variants for Parkinson's disease are located in the α-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.
Formatted abstract
The best validated susceptibility variants for Parkinson's disease are located in the α-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.
Keyword Genetics
Interaction
LRRK2
MAPT
Parkinson's disease
SNCA
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID R01ES10751
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
 
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