High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci

被引：112

作者：

Kim, Kwangwoo ^{[1
,2
,3
,4
]}

Bang, So-Young ^{[1
]}

Lee, Hye-Soon ^{[1
]}

Cho, Soo-Kyung ^{[1
]}

Choi, Chan-Bum ^{[1
]}

Sung, Yoon-Kyoung ^{[1
]}

Kim, Tae-Hwan ^{[1
]}

Jun, Jae-Bum ^{[1
]}

Yoo, Dae Hyun ^{[1
]}

Kang, Young Mo ^{[5
]}

Kim, Seong-Kyu ^{[6
]}

Suh, Chang-Hee ^{[7
]}

Shim, Seung-Cheol ^{[8
]}

Lee, Shin-Seok ^{[9
]}

Lee, Jisoo ^{[10
]}

Chung, Won Tae ^{[11
]}

Choe, Jung-Yoon ^{[6
]}

Shin, Hyoung Doo ^{[12
]}

Lee, Jong-Young ^{[13
]}

Han, Bok-Ghee ^{[13
]}

Nath, Swapan K. ^{[14
]}

Eyre, Steve ^{[15
]}

Bowes, John ^{[15
]}

Pappas, Dimitrios A. ^{[16
]}

Kremer, Joel M. ^{[17
]}

Gonzalez-Gay, Miguel A. ^{[18
]}

Rodriguez-Rodriguez, Luis ^{[19
]}

Arlestig, Lisbeth ^{[20
]}

Okada, Yukinori ^{[2
,3
,4
,21
,22
]}

Diogo, Dorothee ^{[2
,3
,4
]}

Liao, Katherine P. ^{[2
]}

Karlson, Elizabeth W. ^{[2
]}

Raychaudhuri, Soumya ^{[2
,3
,4
,15
]}

Rantapaa-Dahlqvist, Solbritt ^{[20
]}

Martin, Javier ^{[23
]}

Klareskog, Lars ^{[24
,25
]}

Padyukov, Leonid ^{[24
,25
]}

Gregersen, Peter K. ^{[26
]}

Worthington, Jane ^{[14
]}

Greenberg, Jeffrey D. ^{[27
]}

Plenge, Robert M. ^{[2
,3
,4
]}

Bae, Sang-Cheol ^{[1
]}

机构：

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

[2] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Sch Med, Boston, MA 02115 USA

[3] Harvard Univ, Brigham & Womens Hosp, Div Genet, Sch Med, Boston, MA 02115 USA

[4] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[5] Kyungpook Natl Univ, Sch Med, Dept Internal Med, Div Rheumatol, Taegu, South Korea

[6] Catholic Univ, Daegu Sch Med, Dept Internal Med, Div Rheumatol,Arthrit & Autoimmun Res Ctr, Taegu, South Korea

[7] Ajou Univ, Sch Med, Dept Rheumatol, Suwon 441749, South Korea

[8] Chungnam Natl Univ Hosp, Daejeon Rheumatoid & Degenerat Arthrit Ctr, Div Rheumatol, Taejon, South Korea

[9] Chonnam Natl Univ, Med Sch & Hosp, Dept Internal Med, Div Rheumatol, Kwangju, South Korea

[10] Ewha Womans Univ, Sch Med, Dept Internal Med, Div Rheumatol, Seoul, South Korea

[11] Dong A Univ, Dept Internal Med, Div Rheumatol, Pusan, South Korea

[12] Sogang Univ, Dept Life Sci, Seoul, South Korea

[13] Osong Hlth Technol, Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea

[14] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA

[15] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester, Lancs, England

[16] Columbia Univ, Dept Med, Div Rheumatol, New York, NY USA

[17] Ctr Rheumatol, Albany, NY USA

[18] Hosp Marques de Valdecilla, IFIMAV, Dept Rheumatol, Santander, Spain

[19] Hosp Clin San Carlos, Dept Rheumatol, Madrid, Spain

[20] Umea Univ, Dept Clin Med Rheumatoloy, Umea, Sweden

[21] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan

[22] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[23] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain

[24] Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden

[25] Karolinska Univ Hosp Solna, Stockholm, Sweden

[26] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA

[27] NYU, Sch Med, Div Rheumatol, New York, NY USA

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2015年 / 74卷 / 03期

关键词：

GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY BILIARY-CIRRHOSIS; SUSCEPTIBILITY LOCI; GENE-EXPRESSION; MULTIPLE COMMON; CELIAC-DISEASE; POPULATION; METAANALYSIS; VARIANT;

D O I：

10.1136/annrheumdis-2013-204749

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objective A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45 790 European case-control samples. Results We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5x10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusions This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.

引用

页数：8

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