Journal Article

DZNE-2020-03442

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants.

Heckman, M. G. (Corresponding author) ; 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. ; Hattori, N. ; Ioannidis, J. P. A. ; Jasinska-Myga, B. ; Jeon, B. S. ; Kim, Y. J. ; Klein, C. ; Kruger, R.DZNE* ; Kyratzi, E. ; Lin, C.-H. ; Lohmann, K. ; Loriot, M.-A. ; Lynch, T. ; Mellick, G. D. ; Mutez, E. ; Opala, G. ; Park, S. S. ; Petrucci, S. ; Quattrone, A. ; Sharma, M.DZNE* ; Silburn, P. A. ; Sohn, Y. H. ; Stefanis, L. ; Tadic, V. ; Tomiyama, H. ; Uitti, R. J. ; Valente, E. M. ; Vassilatis, D. K. ; Vilariño-Güell, C. ; White, L. R. ; Wirdefeldt, K. ; Wszolek, Z. K. ; Wu, R.-M. ; Xiromerisiou, G. ; Maraganore, D. M. ; Farrer, M. J. ; Ross, O. A. ; Disease, G. E. O. P. ; Maraganore, D. M. ; Farrer, M. J. ; Maraganore, D. M. ; Aasly, J. O. ; Farrer, M. J. ; Elbaz, A. ; Ioannidis, J. P. ; Aasly, J. O. ; Annesi, G. ; Bentivoglio, A. ; Bozi, M. ; Brice, A. ; Carmine-Belin, A. ; Carr, J. ; Carroll, C. ; Chase, B. ; Checkoway, H. ; Chen, S.-D. ; Chung, S. J. ; Cosentino, C. ; Cresswell, S. ; Deutschlaender, A. ; Elbaz, A. ; Ferrarese, C. ; Foroud, T. ; Garraux, G. ; Goldwurm, S. ; Hadjigeorgiou, G. ; Hattori, N. ; Jeon, B. S. ; Kawakami, H. ; Kim, Y. J. ; Kishore, A. ; Klein, C. ; Krainc, D. ; Krygowska-Wajs, A. ; Lay-Son, L. ; Lin, J.-J. ; Maraganore, D. M. ; Mellick, G. ; Morrison, K. E. ; Munhoz, R. P. ; Okubadejo, N. U. ; Opala, G. ; Pastor, P. ; Payami, H. ; Pchelina, S. N. ; Petersen, M. S. ; Puschmann, A. ; Ritz, B. ; Rogaeva, E. ; Sazci, A. ; Slawek, J. ; Stefanis, L. ; Tan, E.-K. ; Toda, T. ; Toft, M. ; Van Broeckhoven, C. ; Wirdefeldt, K. ; Woitalla, D. ; Wszolek, Z. K. ; Zimprich, A.

2014
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.neurobiolaging.2013.07.013

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(s): Adolescent (MeSH) ; Adult (MeSH) ; Aged (MeSH) ; Aged, 80 and over (MeSH) ; Asian Continental Ancestry Group: genetics (MeSH) ; European Continental Ancestry Group: genetics (MeSH) ; Female (MeSH) ; Genetic Predisposition to Disease: genetics (MeSH) ; Genetic Variation (MeSH) ; Genotype (MeSH) ; Haplotypes: genetics (MeSH) ; Humans (MeSH) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Parkinson Disease: genetics (MeSH) ; Parkinson Disease: prevention & control (MeSH) ; Protein-Serine-Threonine Kinases: genetics (MeSH) ; Risk (MeSH) ; Young Adult (MeSH) ; alpha-Synuclein: genetics (MeSH) ; tau Proteins: genetics (MeSH) ; MAPT protein, human ; SNCA protein, human ; alpha-Synuclein ; tau Proteins ; LRRK2 protein, human ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Protein-Serine-Threonine Kinases

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2014

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; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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