Journal
LANCET
Volume 377, Issue 9766, Pages 641-649Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0140-6736(10)62345-8
Keywords
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Categories
Funding
- deCODE
- Eisai
- Merck-Serono
- Cephalon
- Novartis
- National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences
- National Human Genome Research Institute of the National Institutes of Health, Department of Health and Human Services [Z01-AG000949-02, Z01-ES101986]
- US Department of Defense [W81XWH-09-2-0128]
- National Institutes of Health [NS057105, RA024992]
- American Parkinson disease Association (APDA)
- Barnes Jewish Hospital Foundation
- Greater St Louis Chapter of the APDA
- Hersenstichting Nederland
- Neuroscience Campus Amsterdam
- section of medical genomics
- Prinses Beatrix Fonds
- Forschungszentrum fur Umwelt und Gesundheit
- German National Genome Network (German Ministry for Education and Research) [01GS08134]
- German Federal Ministry of Education and Research [NGFN 01GR0468]
- Helmholtz Alliance Mental Health in an Ageing Society [HA-215]
- Helmholtz Association
- French National Agency of Research [ANR-08-MNP-012]
- Landspitali University Hospital
- Icelandic Research Council
- European Community [PIAP-GA-2008-230596]
- Wellcome Trust [083948/Z/07/Z]
- Medical Research Council
- Wellcome Trust disease centre [WT089698/Z/09/Z]
- Parkinson's UK [8047, J-0804]
- Medical Research Council [G0700943]
- Department of Health's National Institute for Health Research Biomedical Research Centres
- Wellcome Trust/Medical Research Council [WT089698]
- Parkinson's Disease Consortium (UKPDC)
- Alzheimers Research UK [ART-PPG2011A-14] Funding Source: researchfish
- Medical Research Council [G0801418B, G0900627, G1100616, G0802462, MC_G0901330, MC_PC_09003, G1100479, G0701075, G0700943, MC_G1000735, G0400017] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0509-10011] Funding Source: researchfish
- Parkinson's UK [J-0901, G-0907, J-0804] Funding Source: researchfish
- MRC [G0900627, G0701075, G0700943, G1100616, G1100479, MC_PC_09003, MC_G1000735, G0802462, MC_G0901330, G0400017] Funding Source: UKRI
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Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease. Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated. Findings The discovery phase consisted of 5333 case and 12 019 control samples, with genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5x10(-8)). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BSTI, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60.3% (95% CI 43.7-69-3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2.51 (95% CI 2.23-2.83) compared with 1.00 in the lowest quintile of disease risk. Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies.
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