title: Lrrk2 G2385R is an ancestral risk factor for Parkinson's disease in Asia.
abstract: The goal of genetic association studies is to identify common (>5%) risk factors in complex disease traits. Herein we describe the first replicable 'functional' risk allele for Parkinson's disease. The leucine-rich repeat kinase 2 (Lrrk2) G2385R substitution is associated with familial parkinsonism, late-, and early-onset Parkinson's disease in ethnic Chinese Taiwanese. Crucially, we provide evidence of identity-by-descent and suggest that Lrrk2 G2385R carriers originate from one ancestor some 4800 years ago, at the start of Chinese civilization. Moreover, our findings demonstrate that common genetic coding variants contribute to Parkinson's disease in a population specific manner which may have important implications for future genome-wide association studies.
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Stone
authors.forename: Chin-Hsien
authors.initials: CH
authors.lastname: Lin
authors.forename: Justus C
authors.initials: JC
authors.lastname: Dächsel
authors.forename: Mary M
authors.initials: MM
authors.lastname: Hulihan
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Haugarvoll
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: Ruey-Meei
authors.initials: RM
authors.lastname: Wu
mesh_terms: D000368:Aged; D001120:Arginine / Q000235:genetics*; D044466:Asian People; D005260:Female; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
chemical_list: D001120:Arginine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine