Year: 2011
Type: review
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<5×10(-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.
Source: PLoS Genetics
Institutions: Georgia Institute of Technology, University College London
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, American Parkinson Disease Association, University of Dundee, Wellcome Trust, National Institute for Health and Care Research, Parkinson's UK, King's College London, European Commission, University of Sheffield, Agence Nationale de la Recherche, Bundesministerium für Bildung und Forschung, Landspítali Háskólasjúkrahús, Hersenstichting, University College London Hospitals NHS Foundation Trust, National Institutes of Health, Medical Research Council, National Institute on Aging, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, Congressionally Directed Medical Research Programs
Awards: G105456294, WTCCC2 core activities., G1432052651, G1546175775, G1623501741, G1826063430, G1955802110, G226565915, WTCCC2 core activities, Verbundprojekt: Nationales Genomforschungsnetz 2: Systematisch-Methodische Plattform GEM: Standort Kiel: PopGen: Populationsrepräsentative Biobank Schleswig-Holstein, G2630206265, Diabetes and Inflammation Laboratory., G2845388095, Prospective studies on Parkinson's disease, G3155125711, A systematic investigation into the pathogenesis and course of Parkinson's syndrome, G3327757157, Identification of new genes causing familial forms of PD, Washington University Center for Translational Neuroscience, G3824181302, G3945394334, G4119534169, G4265316335, Verbundprojekt Funktionelle Genomik der Parkinson-Erkrankung : Genomik, funktionelle Analyse und Bioinformatik (Teilprojekt 1, TP2, TP8, TP9, TP10, TP12, TP16), G4653495942, Dissecting Molecular Genetic Risk Factors in Parkinson's Disease: collaborations with approved protocols with the laboratory of neurogenetics, ERANET 1 NEURON 3: Identification of copy number variants in familial and pathologically proven PD, G5686551843, G5850682332, G6265045657, G6535232462, G6804723138, MECHANISMS OF DEEP BRAIN STIMULATION, Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics., WTCCC2 core activities., Investigations of Dementia in Parkinson Disease, G7310981802, G7616916448, Washington University Institute of Clinical and Translational Sciences (UL1), IAPP on novel genetic and phenotypic markers of Parkinson's disease and Essential Tremor, G8083352728, Identification of copy number variants in familial and pathologically proven PD, G8437048056, G84695714, G8518704759, G8716763575, REFUND CHECK AND WAS DE-OBLIGATED IN THE AMOUNT OF $28,044., Genome wide SNP analysis in Parkinson's disease, A systematic investigation into the pathogenesis and course of Parkinson's syndrome., G9000082987, Genetic and clinical studies of Gaucher disease and other lysosomal disorders
OpenAlex ID: W1483210419