Adolescent; Adult; Aged; Aged, 80 and over; Asian Continental Ancestry Group/genetics; European Continental Ancestry Group/genetics; Female; Genetic Predisposition to Disease/genetics; Genetic Variation; Genotype; Haplotypes/genetics; Humans; Male; Middle Aged; Parkinson Disease/genetics/prevention & control; Protein-Serine-Threonine Kinases/genetics; Risk; Young Adult; alpha-Synuclein/genetics; tau Proteins/genetics; Genetics; Interaction; LRRK2; MAPT; Parkinson's disease; SNCA
Abstract :
[en] The best validated susceptibility variants for Parkinson's disease are located in the alpha-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.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Genetics & genetic processes
Author, co-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
Krüger, Rejko ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit