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A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

Plagnol, V; Nalls, MA; Bras, JM; Hernandez, DG; Sharma, M; Sheerin, UM; ... WTCCC2,; + view all (2011) A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease. PLOS GENET , 7 (6) , Article e1002142. 10.1371/journal.pgen.1002142. Gold open access

Abstract

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.

Type:Article
Title:A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease
Open access status:An open access publication
DOI:10.1371/journal.pgen.1002142
Keywords:GENOME-WIDE ASSOCIATION, FIBROBLAST-GROWTH-FACTOR, ALPHA-SYNUCLEIN, GENE, MUTATIONS, RISK, POPULATION, HAPLOTYPES, VARIANTS, SEQUENCE
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Clinical Neuroscience
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Molecular Neuroscience
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Motor Neuroscience and Movement Disorders
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Neurodegenerative Diseases
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > RLW Institute of Neurological Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment > UCL Genetics Institute

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