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Genome-wide association study confirms extant PD risk loci among the Dutch
Authors:Simón-Sánchez Javier  van Hilten Jacobus J  van de Warrenburg Bart  Post Bart  Berendse Henk W  Arepalli Sampath  Hernandez Dena G  de Bie Rob M A  Velseboer Daan  Scheffer Hans  Bloem Bas  van Dijk Karin D  Rivadeneira Fernando  Hofman Albert  Uitterlinden André G  Rizzu Patrizia  Bochdanovits Zoltan  Singleton Andrew B  Heutink Peter
Affiliation:Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands. j.simonsanchez@vumc.nl
Abstract:In view of the population-specific heterogeneity in reported genetic risk factors for Parkinson's disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514,799 SNPs genotyped in 772 PD cases and 2024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: P = 1.63 × 10(-5), OR = 1.325 and BST1, rs12502586: P = 1.63 × 10(-3), OR = 1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3' and 5' ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: P = 1.22 × 10(-4), OR = 1.51; HLA, rs4248166: P = 4.39 × 10(-5), OR = 1.36; and MAPT, rs3785880: P = 1.9 × 10(-3), OR = 1.19).
Keywords:SNCA   BST1   GAK/DGKQ   HLA   MAPT   PD
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