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

Research output: Contribution to journalArticle

Standard

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; Destée, 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, Eugénie; 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.; Vilariño-Güell, Carles; White, Linda R.; Wirdefeldt, Karin; Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium.

In: Neurobiology of Aging, Vol. 35, No. 1, 01.2014, p. 266.e5-266.e14.

Research output: Contribution to journalArticle

Harvard

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, M-C, 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, C-H, Lohmann, K, Loriot, M-A, Lynch, T, Mellick, GD, Mutez, E, Opala, G, Park, S-S, 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 & Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium 2014, 'Protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants', Neurobiology of Aging, vol. 35, no. 1, pp. 266.e5-266.e14. https://doi.org/10.1016/j.neurobiolaging.2013.07.013

APA

Heckman, M. G., Elbaz, A., Soto-Ortolaza, A. I., Serie, D. J., Aasly, J. O., Annesi, G., ... Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium (2014). 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. https://doi.org/10.1016/j.neurobiolaging.2013.07.013

CBE

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 M-C, 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 C-H, Lohmann K, Loriot M-A, Lynch T, Mellick GD, Mutez E, Opala G, Park S-S, 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, Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium. 2014. 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. https://doi.org/10.1016/j.neurobiolaging.2013.07.013

MLA

Vancouver

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 ; Destée, 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, Eugénie ; 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. ; Vilariño-Güell, Carles ; White, Linda R. ; Wirdefeldt, Karin ; Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium. / Protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants. In: Neurobiology of Aging. 2014 ; Vol. 35, No. 1. pp. 266.e5-266.e14.

RIS

TY - JOUR

T1 - 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 - Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium

AU - Puschmann, Andreas

N1 - Andreas Puschmann is included in Group Author

PY - 2014/1

Y1 - 2014/1

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.

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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Asian Continental Ancestry Group

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2

KW - Male

KW - Middle Aged

KW - Parkinson Disease

KW - Protein-Serine-Threonine Kinases

KW - Risk

KW - Young Adult

KW - alpha-Synuclein

KW - tau Proteins

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.neurobiolaging.2013.07.013

DO - 10.1016/j.neurobiolaging.2013.07.013

M3 - Article

VL - 35

SP - 266.e5-266.e14

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 1558-1497

IS - 1

ER -