title: 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.
authors: Section of Biostatistics, Mayo Clinic, Jacksonville, FL, USA. Electronic address: heckman.michael@mayo.edu.
authors: Michael G
authors: MG
authors: Heckman
authors: Alexis
authors: A
authors: Elbaz
authors: Alexandra I
authors: AI
authors: Soto-Ortolaza
authors: Daniel J
authors: DJ
authors: Serie
authors: Jan O
authors: JO
authors: Aasly
authors: Grazia
authors: G
authors: Annesi
authors: Georg
authors: G
authors: Auburger
authors: Justin A
authors: JA
authors: Bacon
authors: Magdalena
authors: M
authors: Boczarska-Jedynak
authors: Maria
authors: M
authors: Bozi
authors: Laura
authors: L
authors: Brighina
authors: Marie-Christine
authors: MC
authors: Chartier-Harlin
authors: Efthimios
authors: E
authors: Dardiotis
authors: Alain
authors: A
authors: Destée
authors: Carlo
authors: C
authors: Ferrarese
authors: Alessandro
authors: A
authors: Ferraris
authors: Brian
authors: B
authors: Fiske
authors: Suzana
authors: S
authors: Gispert
authors: Georgios M
authors: GM
authors: Hadjigeorgiou
authors: Nobutaka
authors: N
authors: Hattori
authors: John P A
authors: JP
authors: Ioannidis
authors: Barbara
authors: B
authors: Jasinska-Myga
authors: Beom S
authors: BS
authors: Jeon
authors: Yun Joong
authors: YJ
authors: Kim
authors: Christine
authors: C
authors: Klein
authors: Rejko
authors: R
authors: Kruger
authors: Elli
authors: E
authors: Kyratzi
authors: Chin-Hsien
authors: CH
authors: Lin
authors: Katja
authors: K
authors: Lohmann
authors: Marie-Anne
authors: MA
authors: Loriot
authors: Timothy
authors: T
authors: Lynch
authors: George D
authors: GD
authors: Mellick
authors: Eugénie
authors: E
authors: Mutez
authors: Grzegorz
authors: G
authors: Opala
authors: Sung Sup
authors: SS
authors: Park
authors: Simona
authors: S
authors: Petrucci
authors: Aldo
authors: A
authors: Quattrone
authors: Manu
authors: M
authors: Sharma
authors: Peter A
authors: PA
authors: Silburn
authors: Young Ho
authors: YH
authors: Sohn
authors: Leonidas
authors: L
authors: Stefanis
authors: Vera
authors: V
authors: Tadic
authors: Hiroyuki
authors: H
authors: Tomiyama
authors: Ryan J
authors: RJ
authors: Uitti
authors: Enza Maria
authors: EM
authors: Valente
authors: Demetrios K
authors: DK
authors: Vassilatis
authors: Carles
authors: C
authors: Vilariño-Güell
authors: Linda R
authors: LR
authors: White
authors: Karin
authors: K
authors: Wirdefeldt
authors: Zbigniew K
authors: ZK
authors: Wszolek
authors: Ruey-Meei
authors: RM
authors: Wu
authors: Georgia
authors: G
authors: Xiromerisiou
authors: Demetrius M
authors: DM
authors: Maraganore
authors: Matthew J
authors: MJ
authors: Farrer
authors: Owen A
authors: OA
authors: Ross
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics* / Q000517:prevention & control*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012306:Risk; D044465:White People / Q000235:genetics; D055815:Young Adult; D051844:alpha-Synuclein / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Genetics; Interaction; LRRK2; MAPT; Parkinson's disease; SNCA
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