Genome-wide association study reveals genetic risk underlying Parkinson's disease
Document Type
Article
Abstract
We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding alpha-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 x 10(-16)) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 x 10(-16)). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 x 10(-8)) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.
Medical Subject Headings
Cohort Studies; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Japan; Parkinson Disease (epidemiology, genetics); Risk Factors
Publication Date
12-1-2009
Publication Title
Nature genetics
E-ISSN
1546-1718
Volume
41
Issue
12
First Page
1308
Last Page
12
PubMed ID
19915575
Digital Object Identifier (DOI)
10.1038/ng.487
Recommended Citation
Simón-Sánchez, Javier; Schulte, Claudia; Bras, Jose M.; Sharma, Manu; Gibbs, J Raphael; Berg, Daniela; Paisan-Ruiz, Coro; Lichtner, Peter; Scholz, Sonja W.; Hernandez, Dena G.; Krüger, Rejko; Federoff, Monica; Klein, Christine; Goate, Alison; Perlmutter, Joel; Bonin, Michael; Nalls, Michael A.; Illig, Thomas; Gieger, Christian; Houlden, Henry; Steffens, Michael; Okun, Michael S.; Racette, Brad A.; Cookson, Mark R.; Foote, Kelly D.; Fernandez, Hubert H.; Traynor, Bryan J.; Schreiber, Stefan; Arepalli, Sampath; Zonozi, Ryan; Gwinn, Katrina; and van der Brug, Marcel, "Genome-wide association study reveals genetic risk underlying Parkinson's disease" (2009). Neurology. 1131.
https://scholar.barrowneuro.org/neurology/1131