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

Research output: Contribution to journalArticle


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.",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Asian Continental Ancestry Group, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Haplotypes, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Male, Middle Aged, Parkinson Disease, Protein-Serine-Threonine Kinases, Risk, Young Adult, alpha-Synuclein, tau Proteins, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
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 Marie-Christine Chartier-Harlin 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 Chin-Hsien Lin and Katja Lohmann and Marie-Anne Loriot and Timothy Lynch and Mellick, {George D.} and Eug{\'e}nie Mutez and Grzegorz Opala and Sung-Sup Park 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 {Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium} and Andreas Puschmann",
note = "Andreas Puschmann is included in Group Author",
year = "2014",
month = "1",
doi = "10.1016/j.neurobiolaging.2013.07.013",
language = "English",
volume = "35",
pages = "266.e5--266.e14",
journal = "Neurobiology of Aging",
issn = "1558-1497",
publisher = "Elsevier",
number = "1",