Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

被引：759

作者：

Cortes, Adrian ^{[1
]}

Hadler, Johanna ^{[1
]}

Pointon, Jenny P. ^{[2
]}

Robinson, Philip C. ^{[1
]}

Karaderi, Tugce ^{[2
]}

Leo, Paul ^{[1
]}

Cremin, Katie ^{[1
]}

Pryce, Karena ^{[1
]}

Harris, Jessica ^{[1
]}

Lee, Seunghun ^{[3
]}

Joo, Kyung Bin ^{[3
]}

Shim, Seung-Cheol ^{[4
]}

Weisman, Michael ^{[5
]}

Ward, Michael ^{[6
]}

Zhou, Xiaodong ^{[7
]}

Garchon, Henri-Jean ^{[8
,9
]}

Chiocchia, Gilles ^{[8
]}

Nossent, Johannes ^{[10
,11
]}

Lie, Benedicte A. ^{[12
,13
,14
]}

Forre, Oystein ^{[15
]}

Tuomilehto, Jaakko ^{[16
,17
,18
]}

Laiho, Kari ^{[19
]}

Jiang, Lei ^{[20
]}

Liu, Yu ^{[20
]}

Wu, Xin ^{[20
]}

Bradbury, Linda A. ^{[1
]}

Elewaut, Dirk ^{[21
]}

Burgos-Vargas, Ruben ^{[22
]}

Stebbings, Simon ^{[23
]}

Appleton, Louise ^{[2
]}

Farrah, Claire ^{[2
]}

Lau, Jonathan ^{[2
]}

Kenna, Tony J. ^{[1
]}

Haroon, Nigil ^{[24
]}

Ferreira, Manuel A. ^{[25
]}

Yang, Jian ^{[1
]}

Mulero, Juan ^{[26
]}

Fernandez-Sueiro, Jose Luis ^{[27
]}

Gonzalez-Gay, Miguel A. ^{[28
]}

Lopez-Larrea, Carlos ^{[29
,30
]}

Deloukas, Panos ^{[31
]}

Donnelly, Peter ^{[32
]}

Bowness, Paul ^{[2
]}

Gafney, Karl ^{[33
]}

Gaston, Hill ^{[34
]}

Gladman, Dafna D. ^{[35
,36
,37
]}

Rahman, Proton ^{[38
]}

Maksymowych, Walter P. ^{[39
]}

Xu, Huji ^{[20
]}

Crusius, J. Bart A. ^{[40
]}

机构：

[1] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia

[2] Nuffield Orthopaed Ctr, Oxford Musculoskeletal Biomed Res Unit, NIHR, Oxford OX3 7LD, England

[3] Hanyang Univ Hosp Rheumat Dis, Dept Rheumatol, Seoul, South Korea

[4] Eulji Univ Hosp, Div Rheumatol, Dept Med, Taejon, South Korea

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

[6] NIAMSD, US NIH, Bethesda, MD 20892 USA

[7] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA

[8] Univ Paris 05, Inst Cochin, CNRS,INSERM, UMR 8104,U1016, Paris, France

[9] Versailles St Quentin En Yvelines Univ, Hop Ambroise Pare, AP HP, Div Rheumatol, Boulogne, France

[10] Univ Hosp North Norway, Tromso, Norway

[11] Royal Darwin Hosp, Div Med, Darwin, NT, Australia

[12] Univ Oslo, Dept Med Genet, Oslo, Norway

[13] Oslo Univ Hosp, Oslo, Norway

[14] Oslo Univ Hosp, Dept Immunol, Oslo, Norway

[15] Univ Hosp Oslo, Dept Rheumatol, Oslo, Norway

[16] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria

[17] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland

[18] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia

[19] Paijat Hame Cent Hosp, Lahti, Finland

[20] Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Rheumatol & Immunol, Shanghai, Peoples R China

[21] Ghent Univ Hosp, Dept Rheumatol, Ghent, Belgium

[22] Univ Nacl Autonoma Mexico, Fac Med, Hosp Gen Mexico, Dept Rheumatol, Mexico City 04510, DF, Mexico

[23] Univ Otago, Dunedin Sch Med, Dept Med, Dunedin, New Zealand

[24] Toronto Western Hosp, Div Rheumatol, Toronto, ON M5T 2S8, Canada

[25] Univ Queensland, Royal Brisbane Hosp, Queensland Inst Med Res, Herston, Qld, Australia

[26] Hosp Puerta de Hierro, Dept Rheumatol, Madrid, Spain

[27] Complejo Hosp La Coruna, Dept Rheumatol, Inst Invest Biomed A Coruna INIBIC, La Coruna, Spain

[28] Hosp Marques de Valcecilla, IFIMAV, Dept Rheumatol, Santander, Spain

[29] Asturias Cent Univ Hosp, Dept Immunol, Oviedo, Spain

[30] Fdn Renal Inigo Alvarez Toledo, Madrid, Spain

[31] Wellcome Trust Sanger Inst, Cambridge, England

[32] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[33] Norfolk & Norwich Univ Hosp, Dept Rheumatol, Norwich, Norfolk, England

[34] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England

[35] Univ Toronto, Div Rheumatol, Toronto, ON, Canada

[36] Toronto Western Res Inst, Toronto, ON, Canada

[37] Univ Hlth Network, Psoriat Arthrit Program, Toronto, ON, Canada

[38] Mem Univ Newfoundland, St John, NF, Canada

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

[40] Vrije Univ Amsterdam Med Ctr, Dept Med Microbiol & Infect Control, Lab Immunogenet, Amsterdam, Netherlands

[41] Vrije Univ Amsterdam Med Ctr, Dept Rheumatol, Amsterdam, Netherlands

[42] Taipei Vet Gen Hosp, Dept Med, Div Allergy, Taipei, Taiwan

[43] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan

[44] Univ La Sabana, Hosp Mil Cent, Div Rheumatol, Spondyloarthropathy Grp, Bogota, Colombia

[45] Helgelandssykehuset, Mo I Rana, Norway

[46] Univ Nova Lisboa, Fac Ciencias Med, Chron Dis Res Ctr CEDOC, P-1200 Lisbon, Portugal

[47] Norwegian Univ Sci & Technol, Dept Lab Med Childrens & Womens Hlth, N-7034 Trondheim, Norway

[48] Univ Trondheim Hosp, Dept Immunol & Transfus Med, Trondheim, Norway

[49] CSIC, Inst Parasitol Biomed Lopez Neyra, Granada, Spain

[50] MRC, Ctr Causal Anal Translat Epidemiol, Sch Social & Community Med, Bristol, Avon, England

来源：

NATURE GENETICS | 2013年 / 45卷 / 07期

基金：

英国医学研究理事会; 美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会; 英国惠康基金; 中国国家自然科学基金;

关键词：

GENOME-WIDE ASSOCIATION; DISEASE SUSCEPTIBILITY LOCI; HLA CLASS-I; T-CELL; ENDOPLASMIC-RETICULUM; GENETIC SUSCEPTIBILITY; BEHCETS-DISEASE; COMMON; ERAP1; ACTIVATION;

D O I：

10.1038/ng.2667

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

引用

页码：730 / +

页数：11

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