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. Bochdanovits & 82 others M. 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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    Genome-Wide Association Study
    Meta-Analysis
    Single Nucleotide Polymorphism
    Genome
    Population

    Cite this

    Nalls, M. A., Plagnol, V., Hernandez, D. G., Sharma, M., Sheerin, U. M., Saad, M., ... Wood, N. W. (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. https://doi.org/10.1016/S0140-6736(10)62345-8
    Nalls, M.A. ; Plagnol, V. ; Hernandez, D.G. ; Sharma, M. ; Sheerin, U.M. ; Saad, M. ; Simon-Sanchez, J. ; Schulte, C. ; Lesage, S. ; Sveinbjornsdottir, S. ; Arepalli, S. ; Barker, R. ; Ben-Shlomo, Y. ; Berendse, H.W. ; Berg, D. ; Bhatia, K. ; de Bie, R.M.A. ; Biffi, A. ; Bloem, B. ; Bochdanovits, Z. ; Bonin, M. ; Bras, J.M. ; Brockmann, K. ; Brooks, J. ; Burn, D.J. ; Charlesworth, G. ; Chen, H.L. ; Chinnery, P.F. ; Chong, S. ; Clarke, C.E. ; Cookson, M.R. ; Cooper, J.M. ; Corvol, J.C. ; Counsell, C. ; Damier, P. ; Dartigues, J.F. ; Deloukas, P. ; Deuschl, G. ; Dexter, D.T. ; van Dijk, K.D. ; Dillman, A. ; Durif, F. ; Durr, A. ; Edkins, S. ; Evans, J.R. ; Foltynie, T. ; Gao, J.J. ; Gardner, M. ; Gibbs, J.R. ; Goate, A. ; Gray, E. ; Guerreiro, R. ; Gustafsson, O. ; Harris, C ; van Hilten, J.J. ; Hofman, A. ; Hollenbeck, A. ; Holton, J. ; Hu, M. ; Huang, X.M. ; Huber, H. ; Hudson, G. ; Hunt, S.E. ; Huttenlocher, J. ; Illig, T. ; Jonsson, P.V. ; Lambert, J.C. ; Langford, C. ; Lees, A. ; Lichtner, P. ; Limousin, P. ; Lopez, G. ; Lorenz, D. ; McNeill, A. ; Moorby, C. ; Moore, M. ; Morris, H.R. ; Morrison, K.E. ; Mudanohwo, E. ; O'Sullivan, S.S. ; Pearson, J. ; Perlmutter, J.S. ; Petursson, H. ; 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. ; Smith, C. ; Heutink, P. ; Singleton, A.B. ; Wood, N.W. / Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. In: Lancet. 2011 ; Vol. 377, No. 9766. pp. 641-649.
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    title = "Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies",
    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",
    author = "M.A. Nalls and V. Plagnol and D.G. Hernandez and M. Sharma and U.M. Sheerin and M. Saad and J. Simon-Sanchez and C. Schulte and S. Lesage and S. Sveinbjornsdottir and S. Arepalli and R. Barker and Y. Ben-Shlomo and H.W. Berendse and D. Berg and K. Bhatia and {de Bie}, R.M.A. and A. Biffi and B. Bloem and Z. Bochdanovits and M. Bonin and J.M. Bras and K. Brockmann and J. Brooks and D.J. Burn and G. Charlesworth and H.L. Chen and P.F. Chinnery and S. Chong and C.E. Clarke and M.R. Cookson and J.M. Cooper and J.C. Corvol and C. Counsell and P. Damier and J.F. Dartigues and P. Deloukas and G. Deuschl and D.T. Dexter and {van Dijk}, K.D. and A. Dillman and F. Durif and A. Durr and S. Edkins and J.R. Evans and T. Foltynie and J.J. Gao and M. Gardner and J.R. Gibbs and A. Goate and E. Gray and R. Guerreiro and O. Gustafsson and C Harris and {van Hilten}, J.J. and A. Hofman and A. Hollenbeck and J. Holton and M. Hu and X.M. Huang and H. Huber and G. Hudson and S.E. Hunt and J. Huttenlocher and T. Illig and P.V. Jonsson and J.C. Lambert and C. Langford and A. Lees and P. Lichtner and P. Limousin and G. Lopez and D. Lorenz and A. McNeill and C. Moorby and M. Moore and H.R. Morris and K.E. Morrison and E. Mudanohwo and S.S. O'Sullivan and J. Pearson and J.S. Perlmutter and H. Petursson and P. Pollak and B. Post and S. Potter and B. Ravina and T. Revesz and O. Riess and F. Rivadeneira and P. Rizzu and M. Ryten and S. Sawcer and A. Schapira and H. Scheffer and K. Shaw and I. Shoulson and E. Sidransky and C. Smith and P. Heutink and A.B. Singleton and N.W. Wood",
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    pages = "641--649",
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    Nalls, MA, Plagnol, V, Hernandez, DG, Sharma, M, Sheerin, UM, Saad, M, Simon-Sanchez, J, Schulte, C, Lesage, S, Sveinbjornsdottir, S, Arepalli, S, Barker, R, Ben-Shlomo, Y, Berendse, HW, Berg, D, Bhatia, K, de Bie, RMA, Biffi, A, Bloem, B, Bochdanovits, Z, Bonin, M, Bras, JM, Brockmann, K, Brooks, J, Burn, DJ, Charlesworth, G, Chen, HL, 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, Durr, A, Edkins, S, Evans, JR, Foltynie, T, Gao, JJ, Gardner, M, Gibbs, JR, Goate, A, Gray, E, Guerreiro, R, Gustafsson, O, Harris, C, van Hilten, JJ, Hofman, A, Hollenbeck, A, Holton, J, Hu, M, Huang, XM, Huber, H, Hudson, G, Hunt, SE, Huttenlocher, J, Illig, T, Jonsson, PV, Lambert, JC, Langford, C, Lees, A, Lichtner, P, Limousin, P, Lopez, G, Lorenz, D, McNeill, A, Moorby, C, Moore, M, Morris, HR, Morrison, KE, Mudanohwo, E, O'Sullivan, SS, Pearson, J, Perlmutter, JS, Petursson, H, 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, Smith, C, Heutink, P, Singleton, AB & Wood, NW 2011, 'Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies' Lancet, vol. 377, no. 9766, pp. 641-649. https://doi.org/10.1016/S0140-6736(10)62345-8

    Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. / Nalls, M.A.; Plagnol, V.; Hernandez, D.G.; Sharma, M.; Sheerin, U.M.; Saad, M.; Simon-Sanchez, J.; Schulte, C.; Lesage, S.; Sveinbjornsdottir, S.; Arepalli, S.; Barker, R.; Ben-Shlomo, Y.; Berendse, H.W.; Berg, D.; Bhatia, K.; de Bie, R.M.A.; Biffi, A.; Bloem, B.; Bochdanovits, Z.; Bonin, M.; Bras, J.M.; Brockmann, K.; Brooks, J.; Burn, D.J.; Charlesworth, G.; Chen, H.L.; Chinnery, P.F.; Chong, S.; Clarke, C.E.; Cookson, M.R.; Cooper, J.M.; Corvol, J.C.; Counsell, C.; Damier, P.; Dartigues, J.F.; Deloukas, P.; Deuschl, G.; Dexter, D.T.; van Dijk, K.D.; Dillman, A.; Durif, F.; Durr, A.; Edkins, S.; Evans, J.R.; Foltynie, T.; Gao, J.J.; Gardner, M.; Gibbs, J.R.; Goate, A.; Gray, E.; Guerreiro, R.; Gustafsson, O.; Harris, C; van Hilten, J.J.; Hofman, A.; Hollenbeck, A.; Holton, J.; Hu, M.; Huang, X.M.; Huber, H.; Hudson, G.; Hunt, S.E.; Huttenlocher, J.; Illig, T.; Jonsson, P.V.; Lambert, J.C.; Langford, C.; Lees, A.; Lichtner, P.; Limousin, P.; Lopez, G.; Lorenz, D.; McNeill, A.; Moorby, C.; Moore, M.; Morris, H.R.; Morrison, K.E.; Mudanohwo, E.; O'Sullivan, S.S.; Pearson, J.; Perlmutter, J.S.; Petursson, H.; 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.; Smith, C.; Heutink, P.; Singleton, A.B.; Wood, N.W.

    In: Lancet, Vol. 377, No. 9766, 2011, p. 641-649.

    Research output: Contribution to JournalArticleAcademicpeer-review

    TY - JOUR

    T1 - Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies

    AU - Nalls, M.A.

    AU - Plagnol, V.

    AU - Hernandez, D.G.

    AU - Sharma, M.

    AU - Sheerin, U.M.

    AU - Saad, M.

    AU - Simon-Sanchez, J.

    AU - Schulte, C.

    AU - Lesage, S.

    AU - Sveinbjornsdottir, S.

    AU - Arepalli, S.

    AU - Barker, R.

    AU - Ben-Shlomo, Y.

    AU - Berendse, H.W.

    AU - Berg, D.

    AU - Bhatia, K.

    AU - de Bie, R.M.A.

    AU - Biffi, A.

    AU - Bloem, B.

    AU - Bochdanovits, Z.

    AU - Bonin, M.

    AU - Bras, J.M.

    AU - Brockmann, K.

    AU - Brooks, J.

    AU - Burn, D.J.

    AU - Charlesworth, G.

    AU - Chen, H.L.

    AU - Chinnery, P.F.

    AU - Chong, S.

    AU - Clarke, C.E.

    AU - Cookson, M.R.

    AU - Cooper, J.M.

    AU - Corvol, J.C.

    AU - Counsell, C.

    AU - Damier, P.

    AU - Dartigues, J.F.

    AU - Deloukas, P.

    AU - Deuschl, G.

    AU - Dexter, D.T.

    AU - van Dijk, K.D.

    AU - Dillman, A.

    AU - Durif, F.

    AU - Durr, A.

    AU - Edkins, S.

    AU - Evans, J.R.

    AU - Foltynie, T.

    AU - Gao, J.J.

    AU - Gardner, M.

    AU - Gibbs, J.R.

    AU - Goate, A.

    AU - Gray, E.

    AU - Guerreiro, R.

    AU - Gustafsson, O.

    AU - Harris, C

    AU - van Hilten, J.J.

    AU - Hofman, A.

    AU - Hollenbeck, A.

    AU - Holton, J.

    AU - Hu, M.

    AU - Huang, X.M.

    AU - Huber, H.

    AU - Hudson, G.

    AU - Hunt, S.E.

    AU - Huttenlocher, J.

    AU - Illig, T.

    AU - Jonsson, P.V.

    AU - Lambert, J.C.

    AU - Langford, C.

    AU - Lees, A.

    AU - Lichtner, P.

    AU - Limousin, P.

    AU - Lopez, G.

    AU - Lorenz, D.

    AU - McNeill, A.

    AU - Moorby, C.

    AU - Moore, M.

    AU - Morris, H.R.

    AU - Morrison, K.E.

    AU - Mudanohwo, E.

    AU - O'Sullivan, S.S.

    AU - Pearson, J.

    AU - Perlmutter, J.S.

    AU - Petursson, H.

    AU - Pollak, P.

    AU - Post, B.

    AU - Potter, S.

    AU - Ravina, B.

    AU - Revesz, T.

    AU - Riess, O.

    AU - Rivadeneira, F.

    AU - Rizzu, P.

    AU - Ryten, M.

    AU - Sawcer, S.

    AU - Schapira, A.

    AU - Scheffer, H.

    AU - Shaw, K.

    AU - Shoulson, I.

    AU - Sidransky, E.

    AU - Smith, C.

    AU - Heutink, P.

    AU - Singleton, A.B.

    AU - Wood, N.W.

    PY - 2011

    Y1 - 2011

    N2 - 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

    AB - 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

    U2 - 10.1016/S0140-6736(10)62345-8

    DO - 10.1016/S0140-6736(10)62345-8

    M3 - Article

    VL - 377

    SP - 641

    EP - 649

    JO - Lancet

    JF - Lancet

    SN - 0140-6736

    IS - 9766

    ER -