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

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

Research output: Contribution to journalArticlepeer-review

1238 Scopus citations

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 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, 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.

Original languageEnglish
Pages (from-to)1308-1312
Number of pages5
JournalNature Genetics
Volume41
Issue number12
DOIs
StatePublished - Dec 2009

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