期刊
NATURE GENETICS
卷 45, 期 6, 页码 664-+出版社
NATURE PORTFOLIO
DOI: 10.1038/ng.2614
关键词
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资金
- US National Institutes of Health (NIH) [RC1-AR-058587, U01-AI-067150S1]
- US NIH [N01-AR-42272, P01-AR-048929, P30-AR-473639, K23-AR-50177, R01-AR-060893, U01 DK062418, RC2AR059092, DK062431, DK062422, DK062420, DK062432, DK062423, DK062413, DK062429]
- Arthritis Foundation
- Val A. Browning Charitable Foundation in Salt Lake City, Utah
- Marcus Foundation, Inc., in Atlanta, Georgia
- Federal Ministry of Education and Research, Germany (BMBF) [01GM0907, 01 ZZ 0403]
- Arthritis Research UK [17552]
- Sparks, UK [08ICH09]
- Big Lottery Fund, UK [RG/1/010135231]
- Wake Forest School of Medicine Center for Public Health Genomics
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R01-AR-057106]
- NIH from NIAMS [N01-AR-62277, P30-GM-103510, U19-AI-082714, P30-AR-053483]
- National Institute of Allergy and Infectious Diseases (NIAID)
- Wellcome Trust grant [076113/C/04/Z, 068545/Z/01]
- National Institute for Health Research program grant [RP-PG-0310-1002]
- UK Medical Research Council grant [G0000934]
- Juvenile Diabetes Research Foundation International (JDRF)
- Cincinnati Children's Hospital Medical Center
- National Institute of General Medicine Sciences (NIGMS)
- Medical Research Council [G0000934] Funding Source: researchfish
- Sparks Charity [12ICH08, 08ICH09] Funding Source: researchfish
- Versus Arthritis [17287] Funding Source: researchfish
- MRC [G0000934] Funding Source: UKRI
We used the Immunochip array to analyze 2,816 individuals with juvenile idiopathic arthritis (JIA), comprising the most common subtypes (oligoarticular and rheumatoid factor-negative polyarticular JIA), and 13,056 controls. We confirmed association of 3 known JIA risk loci (the human leukocyte antigen (HLA) region, PTPN22 and PTPN2) and identified 14 loci reaching genome-wide significance (P < 5 x 10(-8)) for the first time. Eleven additional new regions showed suggestive evidence of association with JIA (P < 1 x 10(-6)). Dense mapping of loci along with bioinformatics analysis refined the associations to one gene in each of eight regions, highlighting crucial pathways, including the interleukin (IL)-2 pathway, in JIA disease pathogenesis. The entire Immunochip content, the HLA region and the top 27 loci (P < 1 x 10(-6)) explain an estimated 18, 13 and 6% of the risk of JIA, respectively. In summary, this is the largest collection of JIA cases investigated so far and provides new insight into the genetic basis of this childhood autoimmune disease.
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