Nalls, MA and Plagnol, V 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 Arepalli, S and Barker, R 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 Bras, JM 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 Gao, JJ and Gardner, M and Gibbs, JR and Goate, A and Gray, E and Guerreiro, R and Gustafsson, O and Harris, C 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 Lambert, JC 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, HR and Morrison, KE and Mudanohwo, E and O'Sullivan, SS and Pearson, J and Perlmutter, JS and Petursson, H 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 Smith, C and Spencer, CCA and Stefansson, H and Stockton, JD and Strange, A and Talbot, K and Tanner, CM and Tashakkori-Ghanbaria, A and Tison, F and Trabzuni, D and Traynor, BJ and Uitterlinden, AG and Velseboer, D and Vidailhet, M and Walker, R and van de Warrenburg, B and Wickremaratchi, M and Williams, N and Williams-Gray, CH and Winder-Rhodes, S and Stefansson, K and Martinez, M and Hardy, J and Heutink, P and Brice, A and Gasser, T and Singleton, AB and Wood, NW and Int Parkinson Dis Genomics Consort, and Wellcome Trust Case-Control Consor, (2011) Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. LANCET , 377 (9766) 641 - 649. 10.1016/S0140-6736(10)62345-8.
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Abstract
Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease.Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated.Findings The discovery phase consisted of 5333 case and 12 019 control samples, with genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5x10(-8)). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BSTI, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60.3% (95% CI 43.7-69-3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2.51 (95% CI 2.23-2.83) compared with 1.00 in the lowest quintile of disease risk.Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies.
| Type: | Article |
|---|---|
| Title: | Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies |
| DOI: | 10.1016/S0140-6736(10)62345-8 |
| Keywords: | SYNAPTOTAGMIN-XI, COMMON, LOCI, SUSCEPTIBILITY, MUTATIONS, SUGGESTS, REGION, STK39, SNCA |
| UCL classification: | UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Clinical Neuroscience UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Molecular Neuroscience UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Motor Neuroscience and Movement Disorders UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > RLW Institute of Neurological Sciences UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment > UCL Genetics Institute |
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