Lrrk2 G2385R is an ancestral risk factor for Parkinson's disease in Asia.
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.
Farrer
Matthew J
MJ
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Stone
Jeremy T
JT
Lin
Chin-Hsien
CH
Dächsel
Justus C
JC
Hulihan
Mary M
MM
Haugarvoll
Kristoffer
K
Ross
Owen A
OA
Wu
Ruey-Meei
RM
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
D001120:Arginine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine