期刊
PLOS GENETICS
卷 7, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1002142
关键词
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资金
- Wellcome Trust/MRC [WT089698]
- Department of Health NIHR Biomedical Research Centre
- Parkinson's UK [8047, J-0804]
- Medical Research Council [G0700943]
- Wellcome Trust [085475/B/08/Z, 085475/Z/08/Z]
- Wolfson-Royal Society
- UK Medical Research Council [G0901254]
- Reta Lila Weston Trust for Medical Research
- Landspitali University Hospital
- Icelandic Research Council
- European Community [PIAP-GA-2008-230596 MarkMD]
- National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Human Genome Research Institute, 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, RR024992]
- American Parkinson Disease Association (APDA)
- Barnes Jewish Hospital Foundation
- ForschungszentrumfurUmwelt und Gesundheit (GSF)
- German Federal Ministry of Education, Science, Research, and Technology
- State of Bavaria
- German National Genome Network (NGFNplus) [01GS08134]
- German Federal Ministry of Education and Research (BMBF) NGFN [01GR0468]
- Helmholtz Association [HA-215]
- French National Agency of Research [ANR-08-MNP-012]
- National Research Funding Agency [ANR-08-NEUR-004-01]
- MRC [G0400017, MC_G0901330, G0802462, G0800784, MC_PC_09003, G1100479, G0901254, G1100616, G0700943, G0701075, G0501560, G0900627, MC_G1000735] Funding Source: UKRI
- Alzheimers Research UK [ART-PPG2011A-14] Funding Source: researchfish
- Medical Research Council [MC_G1000735, G0700943, G0901254, G0701075, G0501560, G1100479, MC_PC_09003, MC_G0901330, G0900627, G0801418B, G0800784, G1100616, G0400017, G0802462, G0800784B] Funding Source: researchfish
- Parkinson's UK [G-0907, J-0804, J-0901] Funding Source: researchfish
A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stage genotyping array, the ImmunoChip, included a larger set of 1,920 SNPs selected on the basis of the GWA analysis. Here, we analyzed this set of 1,920 SNPs, and we identified five additional PD risk loci (combined p<5x10(-10), PARK16/1q32, STX1B/16p11, FGF20/8p22, STBD1/4q21, and GPNMB/7p15). Two of these five loci have been suggested by previous association studies (PARK16/1q32, FGF20/8p22), and this study provides further support for these findings. Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci.
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