High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

被引：500

作者：

Eyre, Steve ^{[1
,21
]}

Bowes, John ^{[1
,21
]}

Diogo, Dorothee ^{[2
,3
,22
]}

Lee, Annette ^{[4
]}

Barton, Anne ^{[1
,21
]}

Martin, Paul ^{[1
,21
]}

Zhernakova, Alexandra ^{[5
,6
,23
]}

Stahl, Eli ^{[2
,3
,22
]}

Viatte, Sebastien ^{[1
,21
]}

McAllister, Kate ^{[1
,21
]}

Amos, Christopher I. ^{[7
]}

Padyukov, Leonid ^{[8
,9
]}

Toes, Rene E. M. ^{[23
]}

Huizinga, Tom W. J. ^{[23
]}

Wijmenga, Cisca ^{[5
,6
]}

Trynka, Gosia ^{[2
,3
,5
,6
,22
]}

Franke, Lude ^{[5
,6
]}

Westra, Harm-Jan ^{[5
,6
]}

Alfredsson, Lars ^{[10
]}

Hu, Xinli ^{[2
,3
,11
,22
]}

Sandor, Cynthia ^{[2
,3
,22
]}

de Bakker, Paul I. W. ^{[2
,3
,12
,13
,22
]}

Davila, Sonia ^{[14
]}

Khor, Chiea Chuen ^{[14
]}

Heng, Khai Koon ^{[14
]}

Andrews, Robert ^{[15
]}

Edkins, Sarah ^{[15
]}

Hunt, Sarah E. ^{[15
]}

Langford, Cordelia ^{[15
]}

Symmons, Deborah ^{[1
,21
]}

Concannon, Pat ^{[16
]}

Onengut-Gumuscu, Suna ^{[16
]}

Rich, Stephen S. ^{[16
]}

Deloukas, Panos ^{[15
]}

Gonzalez-Gay, Miguel A. ^{[17
]}

Rodriguez-Rodriguez, Luis

Arlsetig, Lisbeth ^{[18
,19
]}

Martin, Javier ^{[20
]}

Rantapaa-Dahlqvist, Solbritt ^{[18
,19
]}

Plenge, Robert M. ^{[2
,3
,22
]}

Raychaudhuri, Soumya ^{[1
,2
,3
,21
,22
]}

Klareskog, Lars ^{[8
,9
]}

Gregersen, Peter K. ^{[4
]}

Worthington, Jane ^{[1
,21
]}

机构：

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

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

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

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

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands

[6] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands

[7] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

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

[9] Karolinska Univ, Hosp Solna, Stockholm, Sweden

[10] Karolinska Inst, Dept Environm Med, Stockholm, Sweden

[11] Harvard Massachusetts Inst Technol Div Hlth Sci &, Boston, MA USA

[12] Univ Med Ctr Utrecht, Dept Epidemiol, Utrecht, Netherlands

[13] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[14] Genome Inst Singapore, Div Human Genet, Singapore, Singapore

[15] Wellcome Trust Sanger Inst, Cambridge, England

[16] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[17] Hosp Marques de Valdecilla, Inst Fdn Invest Marques de Valdecilla, Dept Rheumatol, Santander, Spain

[18] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden

[19] Umea Univ, Dept Rheumatol, Umea, Sweden

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

[21] Cent Manchester Univ Hosp Natl Hlth Serv Fdn Trus, Manchester Acad Hlth Sci Ctr, Manchester Musculoskeletal Biomed Res Unit, Natl Inst Hlth Res, Manchester, Lancs, England

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

[23] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands

来源：

NATURE GENETICS | 2012年 / 44卷 / 12期

基金：

瑞典研究理事会; 美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金;

关键词：

RISK LOCI; METAANALYSIS; ASSOCIATION; EXPRESSION;

D O I：

10.1038/ng.2462

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

引用

页码：1336 / 1340

页数：5

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