Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor

被引：90

作者：

Ban, Maria ^{[1
]}

Goris, An ^{[2
]}

Lorentzen, Aslaug R. ^{[3
,4
]}

Baker, Amie ^{[1
]}

Mihalova, Tania ^{[5
]}

Ingram, Gillian ^{[6
]}

Booth, David R. ^{[7
]}

Heard, Robert N. ^{[7
]}

Stewart, Graeme J. ^{[7
]}

Bogaert, Elke ^{[2
]}

Dubois, Benedicte ^{[2
]}

Harbo, Hanne F. ^{[3
]}

Celius, Elisabeth G. ^{[3
]}

Spurkland, Anne ^{[8
]}

Strange, Richard ^{[5
]}

Hawkins, Clive ^{[5
]}

Robertson, Neil P. ^{[6
]}

Dudbridge, Frank ^{[9
]}

Wason, James ^{[9
]}

De Jager, Philip L. ^{[10
,11
]}

Hafler, David ^{[11
]}

Rioux, John D. ^{[12
,13
]}

Ivinson, Adrian J. ^{[14
]}

McCauley, Jacob L. ^{[15
]}

Pericak-Vance, Margaret ^{[15
]}

Oksenberg, Jorge R. ^{[16
]}

Hauser, Stephen L. ^{[16
]}

Sexton, David ^{[17
]}

Haines, Jonathan ^{[17
]}

Sawcer, Stephen ^{[1
]}

Compston, Alastair ^{[1
]}

机构：

[1] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England

[2] Katholieke Univ Leuven, Sect Expt Neurol, Leuven, Belgium

[3] Univ Oslo, Ulleval Univ Hosp, Fac Div, Dept Neurol, Oslo, Norway

[4] Rikshosp Univ Hosp, Inst Immunol, Oslo, Norway

[5] Keele Univ, Dept Neurol, Sch Med, Stoke On Trent, Staffs, England

[6] Univ Wales Hosp, Dept Neurol, Cardiff, Wales

[7] Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Inst Immunol & Allergy Res, Sydney, NSW 2006, Australia

[8] Univ Oslo, Inst Basic Med Sci, Oslo, Norway

[9] MRC, Biostat Unit, Cambridge CB2 2BW, England

[10] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA USA

[11] Brigham & Womens Hosp, Ctr Neurol Dis, Div Mol Immunol, Boston, MA 02115 USA

[12] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA

[13] MIT, Cambridge, MA 02139 USA

[14] Harvard Univ, Sch Med, Harvard NeuroDiscovery Ctr, Boston, MA USA

[15] Univ Miami, Sch Med, Miami, FL USA

[16] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

[17] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2009年 / 17卷 / 10期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

multiple sclerosis; TYK2; LYSOSOMAL THIOL REDUCTASE; INTERLEUKIN-7; RECEPTOR; DIAGNOSTIC-CRITERIA; GENETIC-BASIS; ASSOCIATION; DISEASES; LINKAGE; POLYMORPHISMS; AUTOIMMUNITY; POPULATION;

D O I：

10.1038/ejhg.2009.41

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In a recent genome-wide association study (GWAS) based on 12 374 non-synonymous single nucleotide polymorphisms we identified a number of candidate multiple sclerosis susceptibility genes. Here, we describe the extended analysis of 17 of these loci undertaken using an additional 4234 patients, 2983 controls and 2053 trio families. In the final analysis combining all available data, we found that evidence for association was substantially increased for one of the 17 loci, rs34536443 from the tyrosine kinase 2 (TYK2) gene (P = 2.7 x 10(-6), odds ratio 1.32 (1.17-1.47)). This single nucleotide polymorphism results in an amino acid substitution (proline to alanine) in the kinase domain of TYK2, which is predicted to influence the levels of phosphorylation and therefore activity of the protein and so is likely to have a functional role in multiple sclerosis. European Journal of Human Genetics (2009) 17, 1309-1313; doi: 10.1038/ejhg.2009.41; published online 18 March 2009

引用

页码：1309 / 1313

页数：5

共 35 条

[1] Inhibitory role of IFN-γ-inducible lysosomal thiol reductase in T cell activation [J].

Barjaktarevic, Igor ;

Rahman, Ayman ;

Radoja, Sasa ;

Bogunovic, Branka ;

Vollmer, Alison ;

Vukmanovic, Stanislav ;

Maric, Maja .

JOURNAL OF IMMUNOLOGY, 2006, 177 (07) :4369-4375

[2] The expanding genetic overlap between multiple sclerosis and type I diabetes [J].

Booth, David R. ;

Heard, Robert N. ;

Stewart, Graeme J. ;

Goris, An ;

Dobosi, Rita ;

Dubois, Benedicte ;

Lorentzen, Aslaug R. ;

Celius, Elisabeth G. ;

Harbo, Hanne F. ;

Spurkland, Anne ;

Olsson, Tomas ;

Kockum, Ingrid ;

Link, Jenny ;

Hillert, Jan ;

Ban, Maria ;

Baker, Amie ;

Sawcer, Stephen ;

Compston, Alastair ;

Mihalova, Tania ;

Strange, Richard ;

Hawkins, Clive ;

Ingram, Gillian ;

Robertson, Neil P. ;

De Jager, Philip L. ;

Hafler, David A. ;

Barcellos, Lisa F. ;

Ivinson, Adrian J. ;

Pericak-Vance, Margaret ;

Oksenberg, Jorge R. ;

Hauser, Stephen L. ;

McCauley, Jacob L. ;

Sexton, David ;

Haines, Jonathan .

GENES AND IMMUNITY, 2009, 10 (01) :11-14

[3]

Compston A., 2005, McAlpine's multiple sclerosis, V4th

[4] Multiple sclerosis [J].

Compston, Alastair ;

Coles, Alasdair .

LANCET, 2008, 372 (9648) :1502-1517

[5] Pedigree disequilibrium tests for multilocus haplotypes [J].

Dudbridge, F .

GENETIC EPIDEMIOLOGY, 2003, 25 (02) :115-121

[6]

Ebers GC, 2000, ANN NEUROL, V48, P927, DOI 10.1002/1531-8249(200012)48:6<927::AID-ANA14>3.0.CO

[7]

2-F

[8] A GENETIC-BASIS FOR FAMILIAL AGGREGATION IN MULTIPLE-SCLEROSIS [J].

EBERS, GC ;

SADOVNICK, AD ;

RISCH, NJ ;

BULMAN, D ;

RICE, GPA ;

HASHIMOTO, SA ;

PATY, D ;

OGER, JJF ;

METZ, L ;

BELL, R ;

WARREN, S ;

HADER, W ;

AUTY, T ;

NATH, A ;

GRAY, T ;

OCONNOR, P ;

NELSON, R ;

FREEDMAN, M ;

BRUNET, D ;

PAULSETH, R ;

FRANCIS, G ;

DUQUETTE, P ;

MURRAY, TJ ;

BAHN, V ;

PRYSEPHILLIPS, W .

NATURE, 1995, 377 (6545) :150-151

[9] Association of polymorphisms across the tyrosine kinase gene, TYK2 in UKSLE families [J].

Graham, D. S. C. ;

Akil, M. ;

Vyse, T. J. .

RHEUMATOLOGY, 2007, 46 (06) :927-930

[10] Interleukin 7 receptor a chain (IL7R) shows allelic and functional association with multiple sclerosis [J].

Gregory, Simon G. ;

Schmidt, Silke ;

Seth, Puneet ;

Oksenberg, Jorge R. ;

Hart, John ;

Prokop, Angela ;

Caillier, Stacy J. ;

Ban, Maria ;

Goris, An ;

Barcellos, Lisa F. ;

Lincoln, Robin ;

McCauley, Jacob L. ;

Sawcer, Stephen J. ;

Compston, D. A. S. ;

Dubois, Benedicte ;

Hauser, Stephen L. ;

Garcia-Blanco, Mariano A. ;

Pericak-Vance, Margaret A. ;

Haines, Jonathan L. .

NATURE GENETICS, 2007, 39 (09) :1083-1091

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