Journal Article

Genome-wide association study reveals genetic risk underlying Parkinson's disease

Hernandez, Dena G, Lichtner, Peter, Okun, Michael S, Goate, Alison, Foote, Kelly D, Steffens, Michael, Sharma, Manu, Illig, Thomas, Traynor, Bryan J, Singleton, Andrew B, Schreiber, Stefan, Riess, Olaf, Hardy, John A, Paisan-Ruiz, Coro, Klein, Christine, Perlmutter, Joel, Zonozi, Ryan, Nalls, Michael A, Park, Yikyung, Schulte, Claudia, Scholz, Sonja W, Gibbs, J Raphael, Wood, Nick W, Gieger, Christian, Lopez, Grisel, Chen, Honglei, Gao, Jianjun, Berg, Daniela, Lorenz, Delia, van der Brug, Marcel, Arepalli, Sampath, Huang, Xuemei, Hollenbeck, Albert, Schatzkin, Arthur, Federoff, Monica, Bonin, Michael, Gwinn, Katrina, Cookson, Mark R, Deuschl, Günther, Bras, Jose M, Chanock, Stephen J, Houlden, Henry, Simón-Sánchez, Javier, Racette, Brad A, Krüger, Rejko, Gasser, Thomas, Fernandez, Hubert H

2009

Overview

Andrew Singleton, Thomas Gasser and colleagues report results of a genome-wide association study of Parkinson's disease among individuals of European ancestry. They find genome-wide significant associations at two loci, SNCA and MAPT , and provide supporting evidence for a new risk locus on 1q32. 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 α-synuclein ( SNCA ; rs2736990, OR = 1.23, P = 2.24 × 10 −16 ) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 × 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 1 , 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 × 10 −8 ) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 × 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Agriculture / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chromosomes / Cohort Studies / Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases / Education / Environmental health / Fundamental and applied biological sciences. Psychology / Gene Frequency / Gene Function / Genetic aspects / Genetic Predisposition to Disease / Genetic susceptibility / Genetic variance / Genetic Variation / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study / Heterogeneity / Human Genetics / Humans / Japan / letter / Medical sciences / Nervous system (semeiology, syndromes) / Nervous system as a whole / Neurological disorders / Neurology / Parkinson Disease - epidemiology / Parkinson Disease - genetics / Parkinson's disease / Quality control / Regression analysis / Risk Factors / Single nucleotide polymorphisms