A rare variant of the TYK2 gene is confirmed to be associated with multiple sclerosis

被引：55

作者：

Mero, Inger-Lise ^{[1
,2
]}

Lorentzen, Aslaug R. ^{[2
,3
]}

Ban, Maria ^{[4
]}

Smestad, Cathrine ^{[1
]}

Celius, Elisabeth G. ^{[1
]}

Aarseth, Jan H. ^{[5
]}

Myhr, Kjell-Morten ^{[5
]}

Link, Jenny ^{[6
]}

Hillert, Jan ^{[6
]}

Olsson, Tomas ^{[7
,8
]}

Kockum, Ingrid ^{[7
,8
]}

Masterman, Thomas ^{[6
]}

Oturai, Annette Bang ^{[9
]}

Sondergaard, Helle Bach ^{[9
]}

Sellebjerg, Finn ^{[9
]}

Saarela, Janna ^{[10
]}

Kemppinen, Anu ^{[10
]}

Elovaara, Irina ^{[11
,12
]}

Spurkland, Anne ^{[13
]}

Dudbridge, Frank ^{[14
]}

Lie, Benedicte A. ^{[2
]}

Harbo, Hanne F. ^{[1
,3
]}

机构：

[1] Oslo Univ Hosp, Dept Neurol, N-0407 Oslo, Norway

[2] Oslo Univ Hosp, Rikshosp, Inst Immunol, N-0407 Oslo, Norway

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

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

[5] Haukeland Hosp, Norwegian Multiple Sclerosis Registry & Biobank, Dept Neurol, N-5021 Bergen, Norway

[6] Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, Multiple Sclerosis Res Grp, Stockholm, Sweden

[7] Karolinska Univ Hosp, Neuroimmunol Unit, Dept Clin Neurosci, Solna, Sweden

[8] Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Solna, Sweden

[9] Copenhagen Univ Hosp, Dept Neurol, Danish Multiple Sclerosis Res Ctr, Copenhagen, Denmark

[10] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[11] Tampere Univ Hosp, Dept Neurol, Tampere, Finland

[12] Univ Tampere, Neuroimmunol Unit, Sch Med, FIN-33101 Tampere, Finland

[13] Univ Oslo, Inst Basal Med Sci, Oslo, Norway

[14] MRC Biostat Unit, Cambridge, England

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2010年 / 18卷 / 04期

基金：

瑞典研究理事会; 芬兰科学院;

关键词：

TYK2; MS; ns-SNP; autoimmune disease; GENOME-WIDE ASSOCIATION; DIAGNOSTIC-CRITERIA; SUSCEPTIBILITY; REPLICATION; GUIDELINES;

D O I：

10.1038/ejhg.2009.195

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：

A rare functional variant within the TYK2 gene (rs34536443) has been reported as protective in multiple sclerosis (MS) in recent studies. However, because of the low frequency of the minor allele (minor allele frequency 0.04), genome-wide significant association has been hard to establish. We genotyped 5429 Nordic MS cases and 6167 healthy controls for this TYK2 non-synonymous single-nucleotide polymorphism (ns-SNP), and combined the Nordic genotype data with raw genotypes from previous studies. The combined Nordic analysis showed significant association with MS (P=5x10(-4), odds ratio (OR) 0.78), and by mega-analysis of 10 642 MS patients, 10 620 controls and 2110 MS trios, the association at genome-wide significance level (P=5.08x10(-9), OR 0.77) was shown. European Journal of Human Genetics (2010) 18, 502-504; doi:10.1038/ejhg.2009.195; published online 4 November 2009

引用

页码：502 / 504

页数：3

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