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

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

doi:10.1016/j.neurobiolaging.2013.07.013

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

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

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. © 2014 Elsevier Inc.

Original language	English
Title of host publication	Neurobiology of Aging
Publication date	01.01.2014
Pages	5 - 266
Article number	35
ISBN (Print)	5106432685
DOIs	https://doi.org/10.1016/j.neurobiolaging.2013.07.013
Publication status	Published - 01.01.2014

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http://www.mendeley.com/research/protective-effect-lrrk2-pr1398h-risk-parkinsons-disease-independent-mapt-snca-variants

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Heckman, M. G., Elbaz, A., Soto-Ortolaza, A. I., Serie, D. J., Aasly, J. O., Annesi, G., Auburger, G., Bacon, J. A., Boczarska-Jedynak, M., Bozi, M., Brighina, L., Chartier-Harlin, M. C., Dardiotis, E., Destée, A., Ferrarese, C., Ferraris, A., Fiske, B., Gispert, S., Hadjigeorgiou, G. M., ... Ross, O. A. (2014). The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants. In Neurobiology of Aging (pp. 5 - 266). Article 35 (Neurobiology of Aging; Vol. 35). https://doi.org/10.1016/j.neurobiolaging.2013.07.013

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

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. {\textcopyright} 2014 Elsevier Inc.",

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

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doi = "10.1016/j.neurobiolaging.2013.07.013",

language = "English",

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Heckman, MG, Elbaz, A, Soto-Ortolaza, AI, Serie, DJ, Aasly, JO, Annesi, G, Auburger, G, Bacon, JA, Boczarska-Jedynak, M, Bozi, M, Brighina, L, Chartier-Harlin, MC, Dardiotis, E, Destée, A, Ferrarese, C, Ferraris, A, Fiske, B, Gispert, S, Hadjigeorgiou, GM, Hattori, N, Ioannidis, JPA, Jasinska-Myga, B, Jeon, BS, Kim, YJ, Klein, C, Kruger, R, Kyratzi, E, Lin, CH, Lohmann, K, Loriot, MA, Lynch, T, Mellick, GD, Mutez, E, Opala, G, Park, SS, Petrucci, S, Quattrone, A, Sharma, M, Silburn, PA, Sohn, YH, Stefanis, L, Tadic, V, Tomiyama, H, Uitti, RJ, Valente, EM, Vassilatis, DK, Vilariño-Güell, C, White, LR, Wirdefeldt, K, Wszolek, ZK, Wu, RM, Xiromerisiou, G, Maraganore, DM, Farrer, MJ & Ross, OA 2014, The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants. in Neurobiology of Aging., 35, Neurobiology of Aging, vol. 35, pp. 5 - 266. https://doi.org/10.1016/j.neurobiolaging.2013.07.013

TY - CHAP

T1 - The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants

AU - Heckman, Michael G.

AU - Elbaz, Alexis

AU - Soto-Ortolaza, Alexandra I.

AU - Serie, Daniel J.

AU - Aasly, Jan O.

AU - Annesi, Grazia

AU - Auburger, Georg

AU - Bacon, Justin A.

AU - Boczarska-Jedynak, Magdalena

AU - Bozi, Maria

AU - Brighina, Laura

AU - Chartier-Harlin, Marie Christine

AU - Dardiotis, Efthimios

AU - Destée, Alain

AU - Ferrarese, Carlo

AU - Ferraris, Alessandro

AU - Fiske, Brian

AU - Gispert, Suzana

AU - Hadjigeorgiou, Georgios M.

AU - Hattori, Nobutaka

AU - Ioannidis, John P.A.

AU - Jasinska-Myga, Barbara

AU - Jeon, Beom S.

AU - Kim, Yun Joong

AU - Klein, Christine

AU - Kruger, Rejko

AU - Kyratzi, Elli

AU - Lin, Chin Hsien

AU - Lohmann, Katja

AU - Loriot, Marie Anne

AU - Lynch, Timothy

AU - Mellick, George D.

AU - Mutez, Eugénie

AU - Opala, Grzegorz

AU - Park, Sung Sup

AU - Petrucci, Simona

AU - Quattrone, Aldo

AU - Sharma, Manu

AU - Silburn, Peter A.

AU - Sohn, Young Ho

AU - Stefanis, Leonidas

AU - Tadic, Vera

AU - Tomiyama, Hiroyuki

AU - Uitti, Ryan J.

AU - Valente, Enza Maria

AU - Vassilatis, Demetrios K.

AU - Vilariño-Güell, Carles

AU - White, Linda R.

AU - Wirdefeldt, Karin

AU - Wszolek, Zbigniew K.

AU - Wu, Ruey Meei

AU - Xiromerisiou, Georgia

AU - Maraganore, Demetrius M.

AU - Farrer, Matthew J.

AU - Ross, Owen A.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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. © 2014 Elsevier Inc.

AB - 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. © 2014 Elsevier Inc.

U2 - 10.1016/j.neurobiolaging.2013.07.013

DO - 10.1016/j.neurobiolaging.2013.07.013

M3 - Chapter

C2 - 23962496

SN - 5106432685

T3 - Neurobiology of Aging

SP - 5

EP - 266

BT - Neurobiology of Aging

ER -

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

Abstract

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