Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population

File Size Format
67423_1.pdf 1878Kb Adobe PDF View
Title Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population
Author Saad, Mohamad; Lesage, Suzanne; Saint-Pierre, Aude; Corvol, Jean-Christophe; Zelenika, Diana; Lambert, Jean-Charles; Vidailhet, Marie; Mellick, George; Lohmann, Ebba; Durif, Franck; Pollak, Pierre; Damier, Philippe; Tison, François; Silburn, Peter Allen; Tzourio, Christophe; Forlani, Sylvie; Loriot, Marie-Anne; Giroud, Maurice; Helmer, Catherine; Portet, Florence; Amouyel, Philippe; Lathrop, Mark; Elbaz, Alexis; Durr, Alexandra; Martinez, Maria; Brice, Alexis
Journal Name Human Molecular Genetics
Year Published 2011
Place of publication United Kingdom
Publisher Oxford University Press
Abstract We performed a three-stage genome-wide association study (GWAS) to identify common Parkinson's disease (PD) risk variants in the European population. The initial genome-wide scan was conducted in a French sample of 1039 cases and 1984 controls, using almost 500 000 single nucleotide polymorphisms (SNPs). Two SNPs at SNCA were found to be associated with PD at the genome-wide significance level (P < 3 × 10−8). An additional set of promising and new association signals was identified and submitted for immediate replication in two independent case–control studies of subjects of European descent. We first carried out an in silico replication study using GWAS data from the WTCCC2 PD study sample (1705 cases, 5200 WTCCC controls). Nominally replicated SNPs were further genotyped in a third sample of 1527 cases and 1864 controls from France and Australia. We found converging evidence of association with PD on 12q24 (rs4964469, combined P = 2.4 × 10−7) and confirmed the association on 4p15/BST1 (rs4698412, combined P = 1.8 × 10−6), previously reported in Japanese data. The 12q24 locus includes RFX4, an isoform of which, named RFX4_v3, encodes brain-specific transcription factors that regulate many genes involved in brain morphogenesis and intracellular calcium homeostasis.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1093/hmg/ddq497
Copyright Statement Copyright 2011 Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The definitive publisher-authenticated version: Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population, Human Molecular Genetics, 20 (3): 615-627 is available online at: http://dx.doi.org/10.1093/hmg/ddq497
Volume 20
Issue Number 3
Page from 615
Page to 627
ISSN 1460-2083
Date Accessioned 2011-01-28
Date Available 2012-03-15T06:06:11Z
Language en_US
Research Centre Eskitis Institute for Drug Discovery
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Neurology and Neuromuscular Diseases
URI http://hdl.handle.net/10072/39852
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

Show simple item record

Griffith University copyright notice