Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies

M.A. Nalls, V. Plagnol, D.G. Hernandez, M. Sharma, U.M. Sheerin, M. Saad, J. Simon-Sanchez, C. Schulte, S. Lesage, S. Sveinbjornsdottir, S. Arepalli, R. Barker, Y. Ben-Shlomo, H.W. Berendse, D. Berg, K. Bhatia, R.M.A. de Bie, A. Biffi, B. Bloem, Z. BochdanovitsM. Bonin, J.M. Bras, K. Brockmann, J. Brooks, D.J. Burn, G. Charlesworth, H.L. Chen, P.F. Chinnery, S. Chong, C.E. Clarke, M.R. Cookson, J.M. Cooper, J.C. Corvol, C. Counsell, P. Damier, J.F. Dartigues, P. Deloukas, G. Deuschl, D.T. Dexter, K.D. van Dijk, A. Dillman, F. Durif, A. Durr, S. Edkins, J.R. Evans, T. Foltynie, J.J. Gao, M. Gardner, J.R. Gibbs, A. Goate, E. Gray, R. Guerreiro, O. Gustafsson, C Harris, J.J. van Hilten, A. Hofman, A. Hollenbeck, J. Holton, M. Hu, X.M. Huang, H. Huber, G. Hudson, S.E. Hunt, J. Huttenlocher, T. Illig, P.V. Jonsson, J.C. Lambert, C. Langford, A. Lees, P. Lichtner, P. Limousin, G. Lopez, D. Lorenz, A. McNeill, C. Moorby, M. Moore, H.R. Morris, K.E. Morrison, E. Mudanohwo, S.S. O'Sullivan, J. Pearson, J.S. Perlmutter, H. Petursson, P. Pollak, B. Post, S. Potter, B. Ravina, T. Revesz, O. Riess, F. Rivadeneira, P. Rizzu, M. Ryten, S. Sawcer, A. Schapira, H. Scheffer, K. Shaw, I. Shoulson, E. Sidransky, C. Smith, P. Heutink, A.B. Singleton, N.W. Wood

    Research output: Contribution to JournalArticleAcademicpeer-review

    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 12019 control samples, with genotyped and imputed data at 7689524 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<5×10
    Original languageEnglish
    Pages (from-to)641-649
    JournalLancet
    Volume377
    Issue number9766
    DOIs
    Publication statusPublished - 2011

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