A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

V. Plagnol; M.A. Nalls; J.M. Bras; D.G. Hernandez; M. Sharma; U.M. Sheerin; M. Saad; J. Simon-Sanchez; C. Schulte; S. Lesage; S. Sveinbjornsdottir; P. Amouyel; S. Arepalli; G. Band; R.A. Barker; C. Bellinguez; Y. Ben-Shlomo; H.W. Berendse; D. Berg; K. Bhatia; R.M.A. de Bie; A. Biffi; B. Bloem; Z. Bochdanovits; M. Bonin; 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; C. Freeman; J.J. Gao; M. Gardner; J.R. Gibbs; A. Goate; E. Gray; R. Guerreiro; O. Gustafsson; C Harris; G. Hellenthal; 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; C. Langford; A. Lees; P. Lichtner; P. Limousin; G. Lopez; D. Lorenz; A. McNeill; C. Moorby; M. Moore; H. Morris; K.E. Morrison; E. Mudanohwo; S.S. O'Sullivan; J. Pearson; R. Pearson; J.S. Perlmutter; H. Petursson; M. Pirinen; P. Pollak; B. Post; S. Potter; B. Ravina; T. Revesz; O. Riess; F. Rivadeneira; P. Rizzu; M. Ryten; S. Sawcer; P. Heutink; N.W. Wood; Alexandra Duerr; Anthony Schapira; Hans Scheffer; Karen Shaw; Ira Shoulson; Ellen Sidransky; Rohan de Silva; Colin Smith; Chris C. A. Spencer; Hreinn Stefansson; Stacy Steinberg; Joanna D. Stockton; Amy Strange; Zhan Su; Kevin Talbot; Carlie M. Tanner; Avazeh Tashakkori-Ghanbaria; Francois Tison; Daniah Trabzuni; Bryan J. Traynor; Andre G. Uitterlinden; Jana Vandrovcova; Daan Velseboer; Marie Vidailhet; Damjan Vukcevic; Robert Walker; Bart van de Warrenburg; Michael E. Weale; Mirdhu Wickremaratchi; Nigel Williams; Caroline H. Williams-Gray; Sophie Winder-Rhodes; Kari Stefansson; Maria Martinez; Peter Donnelly; Andrew B. Singleton; John Hardy; Alexis Brice; Thomas Gasser

doi:https://doi.org/10.1371/journal.pgen.1002142

A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

V. Plagnol, M.A. Nalls, J.M. Bras, D.G. Hernandez, M. Sharma, U.M. Sheerin, M. Saad, J. Simon-Sanchez, C. Schulte, S. Lesage, S. Sveinbjornsdottir, P. Amouyel, S. Arepalli, G. Band, R.A. Barker, C. Bellinguez, Y. Ben-Shlomo, H.W. Berendse, D. Berg, K. BhatiaR.M.A. de Bie, A. Biffi, B. Bloem, Z. Bochdanovits, M. Bonin, 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, C. Freeman, J.J. Gao, M. Gardner, J.R. Gibbs, A. Goate, E. Gray, R. Guerreiro, O. Gustafsson, C Harris, G. Hellenthal, 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, C. Langford, A. Lees, P. Lichtner, P. Limousin, G. Lopez, D. Lorenz, A. McNeill, C. Moorby, M. Moore, H. Morris, K.E. Morrison, E. Mudanohwo, S.S. O'Sullivan, J. Pearson, R. Pearson, J.S. Perlmutter, H. Petursson, M. Pirinen, P. Pollak, B. Post, S. Potter, B. Ravina, T. Revesz, O. Riess, F. Rivadeneira, P. Rizzu, M. Ryten, S. Sawcer, P. Heutink, N.W. Wood, Alexandra Duerr, Anthony Schapira, Hans Scheffer, Karen Shaw, Ira Shoulson, Ellen Sidransky, Rohan de Silva, Colin Smith, Chris C. A. Spencer, Hreinn Stefansson, Stacy Steinberg, Joanna D. Stockton, Amy Strange, Zhan Su, Kevin Talbot, Carlie M. Tanner, Avazeh Tashakkori-Ghanbaria, Francois Tison, Daniah Trabzuni, Bryan J. Traynor, Andre G. Uitterlinden, Jana Vandrovcova, Daan Velseboer, Marie Vidailhet, Damjan Vukcevic, Robert Walker, Bart van de Warrenburg, Michael E. Weale, Mirdhu Wickremaratchi, Nigel Williams, Caroline H. Williams-Gray, Sophie Winder-Rhodes, Kari Stefansson, Maria Martinez, Peter Donnelly, Andrew B. Singleton, John Hardy, Alexis Brice, Thomas Gasser

Research output: Contribution to journal › Article › Academic › peer-review

245 Citations (Scopus)

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 <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

Original language	English
Article number	e1002142
Pages (from-to)	e1002142
Journal	PLoS genetics
Volume	7
Issue number	6
DOIs	https://doi.org/10.1371/journal.pgen.1002142
Publication status	Published - 2011

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https://doi.org/10.1371/journal.pgen.1002142

Cite this

Plagnol, V., Nalls, M. A., Bras, J. M., Hernandez, D. G., Sharma, M., Sheerin, U. M., Saad, M., Simon-Sanchez, J., Schulte, C., Lesage, S., Sveinbjornsdottir, S., Amouyel, P., Arepalli, S., Band, G., Barker, R. A., Bellinguez, C., Ben-Shlomo, Y., Berendse, H. W., Berg, D., ... Gasser, T. (2011). A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease. PLoS genetics, 7(6), e1002142. Article e1002142. https://doi.org/10.1371/journal.pgen.1002142

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title = "A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease",

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 <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",

author = "V. Plagnol and M.A. Nalls and J.M. Bras 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 P. Amouyel and S. Arepalli and G. Band and R.A. Barker and C. Bellinguez 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 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 C. Freeman 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 G. Hellenthal 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 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. Morris and K.E. Morrison and E. Mudanohwo and S.S. O'Sullivan and J. Pearson and R. Pearson and J.S. Perlmutter and H. Petursson and M. Pirinen 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 P. Heutink and N.W. Wood and Alexandra Duerr and Anthony Schapira and Hans Scheffer and Karen Shaw and Ira Shoulson and Ellen Sidransky and {de Silva}, Rohan and Colin Smith and Spencer, {Chris C. A.} and Hreinn Stefansson and Stacy Steinberg and Stockton, {Joanna D.} and Amy Strange and Zhan Su and Kevin Talbot and Tanner, {Carlie M.} and Avazeh Tashakkori-Ghanbaria and Francois Tison and Daniah Trabzuni and Traynor, {Bryan J.} and Uitterlinden, {Andre G.} and Jana Vandrovcova and Daan Velseboer and Marie Vidailhet and Damjan Vukcevic and Robert Walker and {van de Warrenburg}, Bart and Weale, {Michael E.} and Mirdhu Wickremaratchi and Nigel Williams and Williams-Gray, {Caroline H.} and Sophie Winder-Rhodes and Kari Stefansson and Maria Martinez and Peter Donnelly and Singleton, {Andrew B.} and John Hardy and Alexis Brice and Thomas Gasser",

year = "2011",

doi = "https://doi.org/10.1371/journal.pgen.1002142",

language = "English",

volume = "7",

pages = "e1002142",

journal = "PLoS genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "6",

}

Plagnol, V, Nalls, MA, Bras, JM, Hernandez, DG, Sharma, M, Sheerin, UM, Saad, M, Simon-Sanchez, J, Schulte, C, Lesage, S, Sveinbjornsdottir, S, Amouyel, P, Arepalli, S, Band, G, Barker, RA, Bellinguez, C, Ben-Shlomo, Y, Berendse, HW, Berg, D, Bhatia, K, de Bie, RMA, Biffi, A, Bloem, B, Bochdanovits, Z, Bonin, M, 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, Freeman, C, Gao, JJ, Gardner, M, Gibbs, JR, Goate, A, Gray, E, Guerreiro, R, Gustafsson, O, Harris, C, Hellenthal, G, 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, 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, Petursson, H, Pirinen, M, Pollak, P, Post, B, Potter, S, Ravina, B, Revesz, T, Riess, O, Rivadeneira, F, Rizzu, P, Ryten, M, Sawcer, S, Heutink, P, Wood, NW, Duerr, A, Schapira, A, Scheffer, H, Shaw, K, Shoulson, I, Sidransky, E, de Silva, R, Smith, C, Spencer, CCA, Stefansson, 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, Stefansson, K, Martinez, M, Donnelly, P, Singleton, AB, Hardy, J, Brice, A & Gasser, T 2011, 'A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease', PLoS genetics, vol. 7, no. 6, e1002142, pp. e1002142. https://doi.org/10.1371/journal.pgen.1002142

TY - JOUR

T1 - A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

AU - Plagnol, V.

AU - Nalls, M.A.

AU - Bras, J.M.

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 - Amouyel, P.

AU - Arepalli, S.

AU - Band, G.

AU - Barker, R.A.

AU - Bellinguez, C.

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 - 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 - Freeman, C.

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 - Hellenthal, G.

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 - 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.

AU - Morrison, K.E.

AU - Mudanohwo, E.

AU - O'Sullivan, S.S.

AU - Pearson, J.

AU - Pearson, R.

AU - Perlmutter, J.S.

AU - Petursson, H.

AU - Pirinen, M.

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 - Heutink, P.

AU - Wood, N.W.

AU - Duerr, Alexandra

AU - Schapira, Anthony

AU - Scheffer, Hans

AU - Shaw, Karen

AU - Shoulson, Ira

AU - Sidransky, Ellen

AU - de Silva, Rohan

AU - Smith, Colin

AU - Spencer, Chris C. A.

AU - Stefansson, Hreinn

AU - Steinberg, Stacy

AU - Stockton, Joanna D.

AU - Strange, Amy

AU - Su, Zhan

AU - Talbot, Kevin

AU - Tanner, Carlie M.

AU - Tashakkori-Ghanbaria, Avazeh

AU - Tison, Francois

AU - Trabzuni, Daniah

AU - Traynor, Bryan J.

AU - Uitterlinden, Andre G.

AU - Vandrovcova, Jana

AU - Velseboer, Daan

AU - Vidailhet, Marie

AU - Vukcevic, Damjan

AU - Walker, Robert

AU - van de Warrenburg, Bart

AU - Weale, Michael E.

AU - Wickremaratchi, Mirdhu

AU - Williams, Nigel

AU - Williams-Gray, Caroline H.

AU - Winder-Rhodes, Sophie

AU - Stefansson, Kari

AU - Martinez, Maria

AU - Donnelly, Peter

AU - Singleton, Andrew B.

AU - Hardy, John

AU - Brice, Alexis

AU - Gasser, Thomas

PY - 2011

Y1 - 2011

N2 - 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

AB - 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

U2 - https://doi.org/10.1371/journal.pgen.1002142

DO - https://doi.org/10.1371/journal.pgen.1002142

M3 - Article

C2 - 21738488

SN - 1553-7390

VL - 7

SP - e1002142

JO - PLoS genetics

JF - PLoS genetics

IS - 6

M1 - e1002142

ER -