Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

A.H. Beecham; N.A. Patsopoulos; D.K. Xifara; M.F. Davis; A. Kemppinen; C.J. Cotsapas; T.S. Shah; C.C.A. Spencer; D.R. Booth; A.N. Goris; A.B. Oturai; J. Saarela; B. Fontaine; B. Hemmer; C.F.C. Martin; F. Zipp; S. D'Alfonso; F. Martinelli-Boneschi; B.V. Taylor; H.F. Harbo; I. Kockum; J. Hillert; T.P. Olsson; M. Ban; J.R. Oksenberg; R.Q. Hintzen; L.F. Barcellos; C. Agliardi; L.S. Alfredsson; M. Alizadeh; C.A. Anderson; R. Andrews; H.B. Søndergaard; A.P. Baker; G. Band; S.E. Baranzini; N. Barizzone; J.C. Barrett; C. Bellenguez; L. Bergamaschi; L. Bernardinelli; A. Berthele; V. Biberacher; T.M.C. Binder; H. Blackburn; I.L. Bomfim; P. Brambilla; S.A. Broadley; B. Brochet; L. Brundin; D. Buck; H. Butzkueven; S.J. Caillier; W. Camu; W. Carpentier; P. Cavalla; E.G. Celius; I. Coman; G. Comi; L. Corrado; L. Cosemans; I. Cournu-Rebeix; B.A.C. Cree; D. Cusi; V. Damotte; G.L. Defer; S.R. Delgado; P. Deloukas; A. Di Sapio; A.T. Dilthey; P.K. Donnelly; B.D. Dubois; M.E. Duddy; S.J. Edkins; I. Elovaara; F. Esposito; N. Evangelou; B. Fiddes; J.G. Field; A. Franke; C.O. Freeman; I.Y. Frohlich; D. Galimberti; C. Gieger; P.A.F.D. Gourraud; C. Graetz; A. Graham; V. Grummel; C. Guaschino; A. Hadjixenofontos; H.H. Hákonarson; C.A. Halfpenny; G. Hall; P. Hall; A. Hamsten; J. Harley; T.P. Harrower; C.P. Hawkins; G. Hellenthal; C.E.M. Hillier; J.C. Hobart; M. Hoshi; S.E. Hunt; M. Jagodić; I. Jelčić; A. Jochim; B. Kendall; Allan Kermode; T.J. Kilpatrick; K.J. Koivisto; I. Konidari; T. Korn; H.C. Kronsbein; C. Langford; M. Larsson; M.G. Lathrop; C. Lebrun-Frénay; J.S. Lechner-Scott; M. Lee; M.A. Leone; V. Leppä; G. Liberatore; B.A. Lie; C.M. Lill; M. Lindén; J. Link; F. Luessi; J.N. Lycke; F.M. Macciardi; S. Männistö; C.P. Manrique; R. Martin; V. Martinelli; D.M.L. Mason; G. Mazibrada; C. Mccabe; I.L. Mero; J. Mescheriakova; L. Moutsianas; K.M. Myhr; G. Nagels; R.S.J. Nicholas; P.C. Nilsson; F. Piehl; M. Pirinen; S.E. Price; H.L. Quach; M.I. Reunanen; W. Robberecht; N.P. Robertson; M.E. Rodegher; D.J. Rog; M. Salvetti; N.C. Schnetz-Boutaud; F.T. Sellebjerg; R.C. Selter; C.A. Schaefer; S. Shaunak; L. Shen; S. Shields; V. Siffrin; M. Slee; P.S. Sørensen; M. Sorosina; M. Sospedra; A. Spurkland; A. Strange; E. Sundqvist; V.N.S. Thijs; J.W. Thorpe; A.F. Ticca; P.J. Tienari; C.M.A. Van Duijn; E.M. Visser; S. Vucic; H. Westerlind; J.S. Wiley; A. Wilkins; J.F. Wilson; J. Winkelmann; J.P. Zajicek; E. Zindler; J.L. Haines; M.A. Pericak-Vance; A.J. Ivinson; G.J. Stewart; D.D. Hafler; S.L. Hauser; A.D. Compston; G.A.T. Mcvean; P.L. De Jager; S.J. Sawcer; J.L. Mccauley

doi:10.1038/ng.2770

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

A.H. Beecham, N.A. Patsopoulos, D.K. Xifara, M.F. Davis, A. Kemppinen, C.J. Cotsapas, T.S. Shah, C.C.A. Spencer, D.R. Booth, A.N. Goris, A.B. Oturai, J. Saarela, B. Fontaine, B. Hemmer, C.F.C. Martin, F. Zipp, S. D'Alfonso, F. Martinelli-Boneschi, B.V. Taylor, H.F. HarboI. Kockum, J. Hillert, T.P. Olsson, M. Ban, J.R. Oksenberg, R.Q. Hintzen, L.F. Barcellos, C. Agliardi, L.S. Alfredsson, M. Alizadeh, C.A. Anderson, R. Andrews, H.B. Søndergaard, A.P. Baker, G. Band, S.E. Baranzini, N. Barizzone, J.C. Barrett, C. Bellenguez, L. Bergamaschi, L. Bernardinelli, A. Berthele, V. Biberacher, T.M.C. Binder, H. Blackburn, I.L. Bomfim, P. Brambilla, S.A. Broadley, B. Brochet, L. Brundin, D. Buck, H. Butzkueven, S.J. Caillier, W. Camu, W. Carpentier, P. Cavalla, E.G. Celius, I. Coman, G. Comi, L. Corrado, L. Cosemans, I. Cournu-Rebeix, B.A.C. Cree, D. Cusi, V. Damotte, G.L. Defer, S.R. Delgado, P. Deloukas, A. Di Sapio, A.T. Dilthey, P.K. Donnelly, B.D. Dubois, M.E. Duddy, S.J. Edkins, I. Elovaara, F. Esposito, N. Evangelou, B. Fiddes, J.G. Field, A. Franke, C.O. Freeman, I.Y. Frohlich, D. Galimberti, C. Gieger, P.A.F.D. Gourraud, C. Graetz, A. Graham, V. Grummel, C. Guaschino, A. Hadjixenofontos, H.H. Hákonarson, C.A. Halfpenny, G. Hall, P. Hall, A. Hamsten, J. Harley, T.P. Harrower, C.P. Hawkins, G. Hellenthal, C.E.M. Hillier, J.C. Hobart, M. Hoshi, S.E. Hunt, M. Jagodić, I. Jelčić, A. Jochim, B. Kendall, Allan Kermode, T.J. Kilpatrick, K.J. Koivisto, I. Konidari, T. Korn, H.C. Kronsbein, C. Langford, M. Larsson, M.G. Lathrop, C. Lebrun-Frénay, J.S. Lechner-Scott, M. Lee, M.A. Leone, V. Leppä, G. Liberatore, B.A. Lie, C.M. Lill, M. Lindén, J. Link, F. Luessi, J.N. Lycke, F.M. Macciardi, S. Männistö, C.P. Manrique, R. Martin, V. Martinelli, D.M.L. Mason, G. Mazibrada, C. Mccabe, I.L. Mero, J. Mescheriakova, L. Moutsianas, K.M. Myhr, G. Nagels, R.S.J. Nicholas, P.C. Nilsson, F. Piehl, M. Pirinen, S.E. Price, H.L. Quach, M.I. Reunanen, W. Robberecht, N.P. Robertson, M.E. Rodegher, D.J. Rog, M. Salvetti, N.C. Schnetz-Boutaud, F.T. Sellebjerg, R.C. Selter, C.A. Schaefer, S. Shaunak, L. Shen, S. Shields, V. Siffrin, M. Slee, P.S. Sørensen, M. Sorosina, M. Sospedra, A. Spurkland, A. Strange, E. Sundqvist, V.N.S. Thijs, J.W. Thorpe, A.F. Ticca, P.J. Tienari, C.M.A. Van Duijn, E.M. Visser, S. Vucic, H. Westerlind, J.S. Wiley, A. Wilkins, J.F. Wilson, J. Winkelmann, J.P. Zajicek, E. Zindler, J.L. Haines, M.A. Pericak-Vance, A.J. Ivinson, G.J. Stewart, D.D. Hafler, S.L. Hauser, A.D. Compston, G.A.T. Mcvean, P.L. De Jager, S.J. Sawcer, J.L. Mccauley

Centre for Neuromuscular and Neurological Disorders (Perron Institute)

Research output: Contribution to journal › Letter

1095 Citations (Scopus)

Abstract

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P <1.0 × 10 -4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P <5.0 × 10 -8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals. © 2013 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	1353-1362
Journal	Nature Genetics
Volume	45
Issue number	11
DOIs	https://doi.org/10.1038/ng.2770
Publication status	Published - 2013

Access to Document

10.1038/ng.2770

Cite this

Beecham, A. H., Patsopoulos, N. A., Xifara, D. K., Davis, M. F., Kemppinen, A., Cotsapas, C. J., Shah, T. S., Spencer, C. C. A., Booth, D. R., Goris, A. N., Oturai, A. B., Saarela, J., Fontaine, B., Hemmer, B., Martin, C. F. C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B. V., ... Mccauley, J. L. (2013). Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nature Genetics, 45(11), 1353-1362. https://doi.org/10.1038/ng.2770

@article{c860d31afe1040d184da79342ca7d0c7,

title = "Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis",

abstract = "Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P <1.0 × 10 -4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P <5.0 × 10 -8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals. {\textcopyright} 2013 Nature America, Inc. All rights reserved.",

author = "A.H. Beecham and N.A. Patsopoulos and D.K. Xifara and M.F. Davis and A. Kemppinen and C.J. Cotsapas and T.S. Shah and C.C.A. Spencer and D.R. Booth and A.N. Goris and A.B. Oturai and J. Saarela and B. Fontaine and B. Hemmer and C.F.C. Martin and F. Zipp and S. D'Alfonso and F. Martinelli-Boneschi and B.V. Taylor and H.F. Harbo and I. Kockum and J. Hillert and T.P. Olsson and M. Ban and J.R. Oksenberg and R.Q. Hintzen and L.F. Barcellos and C. Agliardi and L.S. Alfredsson and M. Alizadeh and C.A. Anderson and R. Andrews and H.B. S{\o}ndergaard and A.P. Baker and G. Band and S.E. Baranzini and N. Barizzone and J.C. Barrett and C. Bellenguez and L. Bergamaschi and L. Bernardinelli and A. Berthele and V. Biberacher and T.M.C. Binder and H. Blackburn and I.L. Bomfim and P. Brambilla and S.A. Broadley and B. Brochet and L. Brundin and D. Buck and H. Butzkueven and S.J. Caillier and W. Camu and W. Carpentier and P. Cavalla and E.G. Celius and I. Coman and G. Comi and L. Corrado and L. Cosemans and I. Cournu-Rebeix and B.A.C. Cree and D. Cusi and V. Damotte and G.L. Defer and S.R. Delgado and P. Deloukas and {Di Sapio}, A. and A.T. Dilthey and P.K. Donnelly and B.D. Dubois and M.E. Duddy and S.J. Edkins and I. Elovaara and F. Esposito and N. Evangelou and B. Fiddes and J.G. Field and A. Franke and C.O. Freeman and I.Y. Frohlich and D. Galimberti and C. Gieger and P.A.F.D. Gourraud and C. Graetz and A. Graham and V. Grummel and C. Guaschino and A. Hadjixenofontos and H.H. H{\'a}konarson and C.A. Halfpenny and G. Hall and P. Hall and A. Hamsten and J. Harley and T.P. Harrower and C.P. Hawkins and G. Hellenthal and C.E.M. Hillier and J.C. Hobart and M. Hoshi and S.E. Hunt and M. Jagodi{\'c} and I. Jel{\v c}i{\'c} and A. Jochim and B. Kendall and Allan Kermode and T.J. Kilpatrick and K.J. Koivisto and I. Konidari and T. Korn and H.C. Kronsbein and C. Langford and M. Larsson and M.G. Lathrop and C. Lebrun-Fr{\'e}nay and J.S. Lechner-Scott and M. Lee and M.A. Leone and V. Lepp{\"a} and G. Liberatore and B.A. Lie and C.M. Lill and M. Lind{\'e}n and J. Link and F. Luessi and J.N. Lycke and F.M. Macciardi and S. M{\"a}nnist{\"o} and C.P. Manrique and R. Martin and V. Martinelli and D.M.L. Mason and G. Mazibrada and C. Mccabe and I.L. Mero and J. Mescheriakova and L. Moutsianas and K.M. Myhr and G. Nagels and R.S.J. Nicholas and P.C. Nilsson and F. Piehl and M. Pirinen and S.E. Price and H.L. Quach and M.I. Reunanen and W. Robberecht and N.P. Robertson and M.E. Rodegher and D.J. Rog and M. Salvetti and N.C. Schnetz-Boutaud and F.T. Sellebjerg and R.C. Selter and C.A. Schaefer and S. Shaunak and L. Shen and S. Shields and V. Siffrin and M. Slee and P.S. S{\o}rensen and M. Sorosina and M. Sospedra and A. Spurkland and A. Strange and E. Sundqvist and V.N.S. Thijs and J.W. Thorpe and A.F. Ticca and P.J. Tienari and {Van Duijn}, C.M.A. and E.M. Visser and S. Vucic and H. Westerlind and J.S. Wiley and A. Wilkins and J.F. Wilson and J. Winkelmann and J.P. Zajicek and E. Zindler and J.L. Haines and M.A. Pericak-Vance and A.J. Ivinson and G.J. Stewart and D.D. Hafler and S.L. Hauser and A.D. Compston and G.A.T. Mcvean and {De Jager}, P.L. and S.J. Sawcer and J.L. Mccauley",

year = "2013",

doi = "10.1038/ng.2770",

language = "English",

volume = "45",

pages = "1353--1362",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group - Macmillan Publishers",

number = "11",

}

Beecham, AH, Patsopoulos, NA, Xifara, DK, Davis, MF, Kemppinen, A, Cotsapas, CJ, Shah, TS, Spencer, CCA, Booth, DR, Goris, AN, Oturai, AB, Saarela, J, Fontaine, B, Hemmer, B, Martin, CFC, Zipp, F, D'Alfonso, S, Martinelli-Boneschi, F, Taylor, BV, Harbo, HF, Kockum, I, Hillert, J, Olsson, TP, Ban, M, Oksenberg, JR, Hintzen, RQ, Barcellos, LF, Agliardi, C, Alfredsson, LS, Alizadeh, M, Anderson, CA, Andrews, R, Søndergaard, HB, Baker, AP, Band, G, Baranzini, SE, Barizzone, N, Barrett, JC, Bellenguez, C, Bergamaschi, L, Bernardinelli, L, Berthele, A, Biberacher, V, Binder, TMC, Blackburn, H, Bomfim, IL, Brambilla, P, Broadley, SA, Brochet, B, Brundin, L, Buck, D, Butzkueven, H, Caillier, SJ, Camu, W, Carpentier, W, Cavalla, P, Celius, EG, Coman, I, Comi, G, Corrado, L, Cosemans, L, Cournu-Rebeix, I, Cree, BAC, Cusi, D, Damotte, V, Defer, GL, Delgado, SR, Deloukas, P, Di Sapio, A, Dilthey, AT, Donnelly, PK, Dubois, BD, Duddy, ME, Edkins, SJ, Elovaara, I, Esposito, F, Evangelou, N, Fiddes, B, Field, JG, Franke, A, Freeman, CO, Frohlich, IY, Galimberti, D, Gieger, C, Gourraud, PAFD, Graetz, C, Graham, A, Grummel, V, Guaschino, C, Hadjixenofontos, A, Hákonarson, HH, Halfpenny, CA, Hall, G, Hall, P, Hamsten, A, Harley, J, Harrower, TP, Hawkins, CP, Hellenthal, G, Hillier, CEM, Hobart, JC, Hoshi, M, Hunt, SE, Jagodić, M, Jelčić, I, Jochim, A, Kendall, B, Kermode, A, Kilpatrick, TJ, Koivisto, KJ, Konidari, I, Korn, T, Kronsbein, HC, Langford, C, Larsson, M, Lathrop, MG, Lebrun-Frénay, C, Lechner-Scott, JS, Lee, M, Leone, MA, Leppä, V, Liberatore, G, Lie, BA, Lill, CM, Lindén, M, Link, J, Luessi, F, Lycke, JN, Macciardi, FM, Männistö, S, Manrique, CP, Martin, R, Martinelli, V, Mason, DML, Mazibrada, G, Mccabe, C, Mero, IL, Mescheriakova, J, Moutsianas, L, Myhr, KM, Nagels, G, Nicholas, RSJ, Nilsson, PC, Piehl, F, Pirinen, M, Price, SE, Quach, HL, Reunanen, MI, Robberecht, W, Robertson, NP, Rodegher, ME, Rog, DJ, Salvetti, M, Schnetz-Boutaud, NC, Sellebjerg, FT, Selter, RC, Schaefer, CA, Shaunak, S, Shen, L, Shields, S, Siffrin, V, Slee, M, Sørensen, PS, Sorosina, M, Sospedra, M, Spurkland, A, Strange, A, Sundqvist, E, Thijs, VNS, Thorpe, JW, Ticca, AF, Tienari, PJ, Van Duijn, CMA, Visser, EM, Vucic, S, Westerlind, H, Wiley, JS, Wilkins, A, Wilson, JF, Winkelmann, J, Zajicek, JP, Zindler, E, Haines, JL, Pericak-Vance, MA, Ivinson, AJ, Stewart, GJ, Hafler, DD, Hauser, SL, Compston, AD, Mcvean, GAT, De Jager, PL, Sawcer, SJ & Mccauley, JL 2013, 'Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis', Nature Genetics, vol. 45, no. 11, pp. 1353-1362. https://doi.org/10.1038/ng.2770

TY - JOUR

T1 - Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

AU - Beecham, A.H.

AU - Patsopoulos, N.A.

AU - Xifara, D.K.

AU - Davis, M.F.

AU - Kemppinen, A.

AU - Cotsapas, C.J.

AU - Shah, T.S.

AU - Spencer, C.C.A.

AU - Booth, D.R.

AU - Goris, A.N.

AU - Oturai, A.B.

AU - Saarela, J.

AU - Fontaine, B.

AU - Hemmer, B.

AU - Martin, C.F.C.

AU - Zipp, F.

AU - D'Alfonso, S.

AU - Martinelli-Boneschi, F.

AU - Taylor, B.V.

AU - Harbo, H.F.

AU - Kockum, I.

AU - Hillert, J.

AU - Olsson, T.P.

AU - Ban, M.

AU - Oksenberg, J.R.

AU - Hintzen, R.Q.

AU - Barcellos, L.F.

AU - Agliardi, C.

AU - Alfredsson, L.S.

AU - Alizadeh, M.

AU - Anderson, C.A.

AU - Andrews, R.

AU - Søndergaard, H.B.

AU - Baker, A.P.

AU - Band, G.

AU - Baranzini, S.E.

AU - Barizzone, N.

AU - Barrett, J.C.

AU - Bellenguez, C.

AU - Bergamaschi, L.

AU - Bernardinelli, L.

AU - Berthele, A.

AU - Biberacher, V.

AU - Binder, T.M.C.

AU - Blackburn, H.

AU - Bomfim, I.L.

AU - Brambilla, P.

AU - Broadley, S.A.

AU - Brochet, B.

AU - Brundin, L.

AU - Buck, D.

AU - Butzkueven, H.

AU - Caillier, S.J.

AU - Camu, W.

AU - Carpentier, W.

AU - Cavalla, P.

AU - Celius, E.G.

AU - Coman, I.

AU - Comi, G.

AU - Corrado, L.

AU - Cosemans, L.

AU - Cournu-Rebeix, I.

AU - Cree, B.A.C.

AU - Cusi, D.

AU - Damotte, V.

AU - Defer, G.L.

AU - Delgado, S.R.

AU - Deloukas, P.

AU - Di Sapio, A.

AU - Dilthey, A.T.

AU - Donnelly, P.K.

AU - Dubois, B.D.

AU - Duddy, M.E.

AU - Edkins, S.J.

AU - Elovaara, I.

AU - Esposito, F.

AU - Evangelou, N.

AU - Fiddes, B.

AU - Field, J.G.

AU - Franke, A.

AU - Freeman, C.O.

AU - Frohlich, I.Y.

AU - Galimberti, D.

AU - Gieger, C.

AU - Gourraud, P.A.F.D.

AU - Graetz, C.

AU - Graham, A.

AU - Grummel, V.

AU - Guaschino, C.

AU - Hadjixenofontos, A.

AU - Hákonarson, H.H.

AU - Halfpenny, C.A.

AU - Hall, G.

AU - Hall, P.

AU - Hamsten, A.

AU - Harley, J.

AU - Harrower, T.P.

AU - Hawkins, C.P.

AU - Hellenthal, G.

AU - Hillier, C.E.M.

AU - Hobart, J.C.

AU - Hoshi, M.

AU - Hunt, S.E.

AU - Jagodić, M.

AU - Jelčić, I.

AU - Jochim, A.

AU - Kendall, B.

AU - Kermode, Allan

AU - Kilpatrick, T.J.

AU - Koivisto, K.J.

AU - Konidari, I.

AU - Korn, T.

AU - Kronsbein, H.C.

AU - Langford, C.

AU - Larsson, M.

AU - Lathrop, M.G.

AU - Lebrun-Frénay, C.

AU - Lechner-Scott, J.S.

AU - Lee, M.

AU - Leone, M.A.

AU - Leppä, V.

AU - Liberatore, G.

AU - Lie, B.A.

AU - Lill, C.M.

AU - Lindén, M.

AU - Link, J.

AU - Luessi, F.

AU - Lycke, J.N.

AU - Macciardi, F.M.

AU - Männistö, S.

AU - Manrique, C.P.

AU - Martin, R.

AU - Martinelli, V.

AU - Mason, D.M.L.

AU - Mazibrada, G.

AU - Mccabe, C.

AU - Mero, I.L.

AU - Mescheriakova, J.

AU - Moutsianas, L.

AU - Myhr, K.M.

AU - Nagels, G.

AU - Nicholas, R.S.J.

AU - Nilsson, P.C.

AU - Piehl, F.

AU - Pirinen, M.

AU - Price, S.E.

AU - Quach, H.L.

AU - Reunanen, M.I.

AU - Robberecht, W.

AU - Robertson, N.P.

AU - Rodegher, M.E.

AU - Rog, D.J.

AU - Salvetti, M.

AU - Schnetz-Boutaud, N.C.

AU - Sellebjerg, F.T.

AU - Selter, R.C.

AU - Schaefer, C.A.

AU - Shaunak, S.

AU - Shen, L.

AU - Shields, S.

AU - Siffrin, V.

AU - Slee, M.

AU - Sørensen, P.S.

AU - Sorosina, M.

AU - Sospedra, M.

AU - Spurkland, A.

AU - Strange, A.

AU - Sundqvist, E.

AU - Thijs, V.N.S.

AU - Thorpe, J.W.

AU - Ticca, A.F.

AU - Tienari, P.J.

AU - Van Duijn, C.M.A.

AU - Visser, E.M.

AU - Vucic, S.

AU - Westerlind, H.

AU - Wiley, J.S.

AU - Wilkins, A.

AU - Wilson, J.F.

AU - Winkelmann, J.

AU - Zajicek, J.P.

AU - Zindler, E.

AU - Haines, J.L.

AU - Pericak-Vance, M.A.

AU - Ivinson, A.J.

AU - Stewart, G.J.

AU - Hafler, D.D.

AU - Hauser, S.L.

AU - Compston, A.D.

AU - Mcvean, G.A.T.

AU - De Jager, P.L.

AU - Sawcer, S.J.

AU - Mccauley, J.L.

PY - 2013

Y1 - 2013

N2 - Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P <1.0 × 10 -4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P <5.0 × 10 -8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals. © 2013 Nature America, Inc. All rights reserved.

AB - Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P <1.0 × 10 -4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P <5.0 × 10 -8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals. © 2013 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.2770

DO - 10.1038/ng.2770

M3 - Letter

SN - 1061-4036

VL - 45

SP - 1353

EP - 1362

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Abstract

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