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

doi:10.1038/ng.2770

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

Journal article

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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. Cotsapas, T.S. Shah, C. Spencer, D. Booth, A. Goris, …

Nature Genetics, Vol.45(11), pp.1353-1360

2013

DOI: https://doi.org/10.1038/ng.2770

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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.

Details

Title: Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
Authors/Creators: A.H. Beecham (Author/Creator)
N.A. Patsopoulos (Author/Creator)
D.K. Xifara (Author/Creator)
M.F. Davis (Author/Creator)
A. Kemppinen (Author/Creator)
C. Cotsapas (Author/Creator)
T.S. Shah (Author/Creator)
C. Spencer (Author/Creator)
D. Booth (Author/Creator)
A. Goris (Author/Creator)
A. Oturai (Author/Creator)
J. Saarela (Author/Creator)
B. Fontaine (Author/Creator)
B. Hemmer (Author/Creator)
C. Martin (Author/Creator)
F. Zipp (Author/Creator)
S. D'Alfonso (Author/Creator)
F. Martinelli-Boneschi (Author/Creator)
B. Taylor (Author/Creator)
H.F. Harbo (Author/Creator)
I. Kockum (Author/Creator)
J. Hillert (Author/Creator)
T. Olsson (Author/Creator)
M. Ban (Author/Creator)
J.R. Oksenberg (Author/Creator)
R. Hintzen (Author/Creator)
L.F. Barcellos (Author/Creator)
C. Agliardi (Author/Creator)
L. Alfredsson (Author/Creator)
M. Alizadeh (Author/Creator)
C. Anderson (Author/Creator)
R. Andrews (Author/Creator)
H.B. Søndergaard (Author/Creator)
A. Baker (Author/Creator)
G. Band (Author/Creator)
S.E. Baranzini (Author/Creator)
N. Barizzone (Author/Creator)
J. Barrett (Author/Creator)
C. Bellenguez (Author/Creator)
L. Bergamaschi (Author/Creator)
L. Bernardinelli (Author/Creator)
A. Berthele (Author/Creator)
V. Biberacher (Author/Creator)
T.M.C. Binder (Author/Creator)
H. Blackburn (Author/Creator)
I.L. Bomfim (Author/Creator)
P. Brambilla (Author/Creator)
S. Broadley (Author/Creator)
B. Brochet (Author/Creator)
L. Brundin (Author/Creator)
D. Buck (Author/Creator)
H. Butzkueven (Author/Creator)
S.J. Caillier (Author/Creator)
W. Camu (Author/Creator)
W. Carpentier (Author/Creator)
P. Cavalla (Author/Creator)
E.G. Celius (Author/Creator)
I. Coman (Author/Creator)
G. Comi (Author/Creator)
L. Corrado (Author/Creator)
L. Cosemans (Author/Creator)
I. Cournu-Rebeix (Author/Creator)
B.A.C. Cree (Author/Creator)
D. Cusi (Author/Creator)
V. Damotte (Author/Creator)
G. Defer (Author/Creator)
S.R. Delgado (Author/Creator)
P. Deloukas (Author/Creator)
A. di Sapio (Author/Creator)
A.T. Dilthey (Author/Creator)
P. Donnelly (Author/Creator)
B. Dubois (Author/Creator)
M. Duddy (Author/Creator)
S. Edkins (Author/Creator)
I. Elovaara (Author/Creator)
F. Esposito (Author/Creator)
N. Evangelou (Author/Creator)
B. Fiddes (Author/Creator)
J. Field (Author/Creator)
A. Franke (Author/Creator)
C. Freeman (Author/Creator)
I.Y. Frohlich (Author/Creator)
D. Galimberti (Author/Creator)
C. Gieger (Author/Creator)
P-A Gourraud (Author/Creator)
C. Graetz (Author/Creator)
A. Graham (Author/Creator)
V. Grummel (Author/Creator)
C. Guaschino (Author/Creator)
A. Hadjixenofontos (Author/Creator)
H. Hakonarson (Author/Creator)
C. Halfpenny (Author/Creator)
G. Hall (Author/Creator)
P. Hall (Author/Creator)
A. Hamsten (Author/Creator)
J. Harley (Author/Creator)
T. Harrower (Author/Creator)
C. Hawkins (Author/Creator)
G. Hellenthal (Author/Creator)
C. Hillier (Author/Creator)
J. Hobart (Author/Creator)
M. Hoshi (Author/Creator)
S.E. Hunt (Author/Creator)
M. Jagodic (Author/Creator)
I. Jelčić (Author/Creator)
A. Jochim (Author/Creator)
B. Kendall (Author/Creator)
A. Kermode (Author/Creator)
T. Kilpatrick (Author/Creator)
K. Koivisto (Author/Creator)
I. Konidari (Author/Creator)
T. Korn (Author/Creator)
H. Kronsbein (Author/Creator)
C. Langford (Author/Creator)
M. Larsson (Author/Creator)
M. Lathrop (Author/Creator)
C. Lebrun-Frenay (Author/Creator)
J. Lechner-Scott (Author/Creator)
M.H. Lee (Author/Creator)
M.A. Leone (Author/Creator)
V. Leppä (Author/Creator)
G. Liberatore (Author/Creator)
B.A. Lie (Author/Creator)
C.M. Lill (Author/Creator)
M. Linden (Author/Creator)
J. Link (Author/Creator)
F. Luessi (Author/Creator)
J. Lycke (Author/Creator)
F. Macciardi (Author/Creator)
S. Männistö (Author/Creator)
C.P. Manrique (Author/Creator)
R. Martin (Author/Creator)
V. Martinelli (Author/Creator)
D. Mason (Author/Creator)
G. Mazibrada (Author/Creator)
C. McCabe (Author/Creator)
I-L Mero (Author/Creator)
J. Mescheriakova (Author/Creator)
L. Moutsianas (Author/Creator)
K-M Myhr (Author/Creator)
G. Nagels (Author/Creator)
R. Nicholas (Author/Creator)
P. Nilsson (Author/Creator)
F. Piehl (Author/Creator)
M. Pirinen (Author/Creator)
S.E. Price (Author/Creator)
H. Quach (Author/Creator)
M. Reunanen (Author/Creator)
W. Robberecht (Author/Creator)
N.P. Robertson (Author/Creator)
M. Rodegher (Author/Creator)
D. Rog (Author/Creator)
M. Salvetti (Author/Creator)
N.C. Schnetz-Boutaud (Author/Creator)
F. Sellebjerg (Author/Creator)
R.C. Selter (Author/Creator)
C. Schaefer (Author/Creator)
S. Shaunak (Author/Creator)
L. Shen (Author/Creator)
S. Shields (Author/Creator)
V. Siffrin (Author/Creator)
M. Slee (Author/Creator)
P.S. Sorensen (Author/Creator)
M. Sorosina (Author/Creator)
M. Sospedra (Author/Creator)
A. Spurkland (Author/Creator)
A. Strange (Author/Creator)
E. Sundqvist (Author/Creator)
V. Thijs (Author/Creator)
J. Thorpe (Author/Creator)
A. Ticca (Author/Creator)
P. Tienari (Author/Creator)
C. van Duijn (Author/Creator)
E.M. Visser (Author/Creator)
S. Vucic (Author/Creator)
H. Westerlind (Author/Creator)
J.S. Wiley (Author/Creator)
A. Wilkins (Author/Creator)
J.F. Wilson (Author/Creator)
J. Winkelmann (Author/Creator)
J. Zajicek (Author/Creator)
E. Zindler (Author/Creator)
J.L. Haines (Author/Creator)
M.A. Pericak-Vance (Author/Creator)
A.J. Ivinson (Author/Creator)
G. Stewart (Author/Creator)
D. Hafler (Author/Creator)
S.L. Hauser (Author/Creator)
A. Compston (Author/Creator)
G. McVean (Author/Creator)
P. De Jager (Author/Creator)
S.J. Sawcer (Author/Creator)
J.L. McCauley (Author/Creator)
Publication Details: Nature Genetics, Vol.45(11), pp.1353-1360
Publisher: Nature Publishing Group
Identifiers: 991005545435807891
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.203 Neuromuscular Disorders; 1.203.147 Multiple Sclerosis
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics