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 GWAS1, 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.
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We thank the subjects involved in this study whose contribution made this work possible. This work used samples and clinical data from the US National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds). This work was supported in part by the Intramural Research Programs of the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, the National Institute of Environmental Health Sciences, the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services; project numbers Z01 AG000949-02 and Z01-ES101986. The KORA research platform (KORA: Cooperative Research in the Region of Augsburg; ) was initiated and financed by the Forschungszentrum für Umwelt und Gesundheit (GSF), which is funded by the German Federal Ministry of Education, Science, Research and Technology and by the State of Bavaria.
The study was additionally funded by the German National Genome Network (NGFNplus #01GS08134; German Ministry for Education and Research) and in addition by the German Federal Ministry of Education and Research (BMBF) NGFN (01GR0468). This work also was supported by the National Institutes of Health NINDS P30NS05710 (Neuroscience Blueprint Grant) and Clinical Sciences Translational Award RR024992 to Washington University in St. Louis and the Greater St. Louis Chapter of the American Parkinson Disease Association. Authors received support from the Medical Research Council, UK.
Supplementary Note, Supplementary Methods, Supplementary Figures 1–8 and Supplementary Tables 1–6.