Plagnol, V and Nalls, MA and Bras, JM and Hernandez, DG and Sharma, M and Sheerin, UM and Saad, M and Simon-Sanchez, J and Schulte, C and Lesage, S and Sveinbjornsdottir, S and Amouyel, P and Arepalli, S and Band, G and Barker, RA and Bellinguez, C and Ben-Shlomo, Y and Berendse, HW and Berg, D and Bhatia, K and de Bie, RMA and Biffi, A and Bloem, B and Bochdanovits, Z and Bonin, M and Brockmann, K and Brooks, J and Burn, DJ and Charlesworth, G and Chen, HL and Chinnery, PF and Chong, S and Clarke, CE and Cookson, MR and Cooper, JM and Corvol, JC and Counsell, C and Damier, P and Dartigues, JF and Deloukas, P and Deuschl, G and Dexter, DT and van Dijk, KD and Dillman, A and Durif, F and Durr, A and Edkins, S and Evans, JR and Foltynie, T and Freeman, C and Gao, JJ and Gardner, M and Gibbs, JR and Goate, A and Gray, E and Guerreiro, R and Gustafsson, O and Harris, C and Hellenthal, G and van Hilten, JJ and Hofman, A and Hollenbeck, A and Holton, J and Hu, M and Huang, XM and Huber, H and Hudson, G and Hunt, SE and Huttenlocher, J and Illig, T and Jonsson, PV and Langford, C and Lees, A and Lichtner, P and Limousin, P and Lopez, G and Lorenz, D and McNeill, A and Moorby, C and Moore, M and Morris, H and Morrison, KE and Mudanohwo, E and O'Sullivan, SS and Pearson, J and Pearson, R and Perlmutter, JS and Petursson, H and Pirinen, M and Pollak, P and Post, B and Potter, S and Ravina, B and Revesz, T and Riess, O and Rivadeneira, F and Rizzu, P and Ryten, M and Sawcer, S and Schapira, A and Scheffer, H and Shaw, K and Shoulson, I and Sidransky, E and de Silva, R and Smith, C and Spencer, CCA and Stefansson, H and Steinberg, S and Stockton, JD and Strange, A and Su, Z and Talbot, K and Tanner, CM and Tashakkori-Ghanbaria, A and Tison, F and Trabzuni, D and Traynor, BJ and Uitterlinden, AG and Vandrovcova, J and Velseboer, D and Vidailhet, M and Vukcevic, D and Walker, R and van de Warrenburg, B and Weale, ME and Wickremaratchi, M and Williams, N and Williams-Gray, CH and Winder-Rhodes, S and Stefansson, K and Martinez, M and Donnelly, P and Singleton, AB and Hardy, J and Heutink, P and Brice, A and Gasser, T and Wood, NW and WTCCC2, (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.
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.
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