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PLoS Genet. 2011 Jun;7(6):e1002142. doi: 10.1371/journal.pgen.1002142. Epub 2011 Jun 30.

A two-stage meta-analysis identifies several new loci for Parkinson's disease.

Collaborators (139)

Plagnol V, Nalls MA, Bras JM, Hernandez DG, Sharma M, Sheerin UM, Saad M, Simón-Sánchez J, Schulte C, Lesage S, Sveinbjörnsdóttir S, Amouyel P, Arepalli S, Band G, Barker RA, Bellinguez C, Ben-Shlomo Y, Berendse HW, Berg D, Bhatia K, de Bie RM, Biffi A, Bloem B, Bochdanovits Z, Bonin M, Brockmann K, Brooks J, Burn DJ, Charlesworth G, Chen H, Chinnery PF, Chong S, Clarke CE, Cookson MR, Cooper JM, Corvol JC, Counsell C, Damier P, Dartigues JF, Deloukas P, Deuschl G, Dexter DT, van Dijk KD, Dillman A, Durif F, Dürr A, Edkins S, Evans JR, Foltynie T, Freeman C, Gao J, Gardner M, Gibbs JR, Goate A, Gray E, Guerreiro R, Gústafsson Ó, Harris C, Hellenthal G, van Hilten JJ, Hofman A, Hollenbeck A, Holton J, Hu M, Huang X, Huber H, Hudson G, Hunt SE, Huttenlocher J, Illig T, Jónsson PV, Langford C, Lees A, Lichtner P, Limousin P, Lopez G, Lorenz D, McNeill A, Moorby C, Moore M, Morris H, Morrison KE, Mudanohwo E, O'Sullivan SS, Pearson J, Pearson R, Perlmutter JS, Pétursson H, Pirinen M, Pollak P, Post B, Potter S, Ravina B, Revesz T, Riess O, Rivadeneira F, Rizzu P, Ryten M, Sawcer S, Schapira A, Scheffer H, Shaw K, Shoulson I, Sidransky E, de Silva R, Smith C, Spencer CC, Stefánsson H, Steinberg S, Stockton JD, Strange A, Su Z, Talbot K, Tanner CM, Tashakkori-Ghanbaria A, Tison F, Trabzuni D, Traynor BJ, Uitterlinden AG, Vandrovcova J, Velseboer D, Vidailhet M, Vukcevic D, Walker R, van de Warrenburg B, Weale ME, Wickremaratchi M, Williams N, Williams-Gray CH, Winder-Rhodes S, Stefánsson K, Martinez M, Donnelly P, Singleton AB, Hardy J, Heutink P, Brice A, Gasser T, Wood NW.

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.

PMID:
21738488
[PubMed - indexed for MEDLINE]
PMCID:
PMC3128098
Free PMC Article

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