Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci

被引：521

作者：

Reveille, John D. ^{[1
]}

Sims, Anne-Marie ^{[13
]}

Danoy, Patrick ^{[13
]}

Evans, David M. ^{[2
]}

Leo, Paul ^{[13
]}

Pointon, Jennifer J. ^{[3
]}

Jin, Rui ^{[1
]}

Zhou, Xiaodong ^{[1
]}

Bradbury, Linda A. ^{[13
]}

Appleton, Louise H. ^{[3
]}

Davis, John C. ^{[4
]}

Diekman, Laura ^{[1
]}

Doan, Tracey ^{[13
]}

Dowling, Alison ^{[13
]}

Duan, Ran ^{[13
]}

Duncan, Emma L. ^{[13
]}

Farrar, Claire ^{[3
]}

Hadler, Johanna ^{[13
]}

Harvey, David ^{[3
]}

Karaderi, Tugce ^{[3
]}

Mogg, Rebecca ^{[5
,6
]}

Pomeroy, Emma ^{[5
,6
]}

Pryce, Karena ^{[13
]}

Taylor, Jacqueline ^{[13
]}

Savage, Laurie ^{[7
]}

Deloukas, Panos ^{[8
]}

Kumanduri, Vasudev ^{[8
]}

Peltonen, Leena ^{[8
]}

Ring, Sue M. ^{[2
]}

Whittaker, Pamela ^{[8
]}

Glazov, Evgeny ^{[13
]}

Thomas, Gethin P. ^{[13
]}

Maksymowych, Walter P. ^{[9
]}

Inman, Robert D. ^{[10
]}

Ward, Michael M. ^{[11
]}

Stone, Millicent A. ^{[5
,6
,10
]}

Weisman, Michael H. ^{[12
]}

Wordsworth, B. Paul ^{[3
]}

Brown, Matthew A. ^{[3
,13
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA

[2] Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England

[3] Univ Oxford, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England

[4] Univ Calif San Francisco, San Francisco, CA 94143 USA

[5] Royal Natl Hosp Rheumat Dis, Natl Hlth Serv Fdn Trust, Bath BA1 1RL, Avon, England

[6] Univ Bath, Bath BA2 7AY, Avon, England

[7] Spondylitis Assoc Amer, Sherman Oaks, CA USA

[8] Wellcome Trust Sanger Inst, Cambridge, England

[9] Univ Alberta, Dept Med, Edmonton, AB, Canada

[10] Univ Toronto, Toronto, ON, Canada

[11] NIAMSD, NIH, Bethesda, MD 20892 USA

[12] Cedars Sinai Med Ctr, Dept Med Rheumatol, Los Angeles, CA 90048 USA

[13] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld, Australia

来源：

NATURE GENETICS | 2010年 / 42卷 / 02期

基金：

英国医学研究理事会; 美国国家卫生研究院; 英国惠康基金;

关键词：

GENETIC-SUSCEPTIBILITY; VARIANTS; DISEASE; RISK; TNF;

D O I：

10.1038/ng.513

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10(-800)), we found association with SNPs in two gene deserts at 2p15 (rs10865331; combined P = 1.9 x 10(-19)) and 21q22 (rs2242944; P = 8.3 x 10(-20)), as well as in the genes ANTXR2 (rs4333130; P = 9.3 x 10(-8)) and IL1R2 (rs2310173; P = 4.8 x 10(-7)). We also replicated previously reported associations at IL23R (rs11209026; P = 9.1 x 10(-14)) and ERAP1 (rs27434; P = 5.3 x 10(-12)). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.

引用

页码：123 / U47

页数：7

共 25 条

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