PMID- 23603761
OWN - NLM
STAT- MEDLINE
DCOM- 20130802
LR  - 20220408
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 45
IP  - 6
DP  - 2013 Jun
TI  - Dense genotyping of immune-related disease regions identifies 14 new 
      susceptibility loci for juvenile idiopathic arthritis.
PG  - 664-9
LID - 10.1038/ng.2614 [doi]
AB  - 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.
FAU - Hinks, Anne
AU  - Hinks A
AD  - Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science 
      Centre, The University of Manchester, Manchester, UK. anne.hinks@manchester.ac.uk
FAU - Cobb, Joanna
AU  - Cobb J
FAU - Marion, Miranda C
AU  - Marion MC
FAU - Prahalad, Sampath
AU  - Prahalad S
FAU - Sudman, Marc
AU  - Sudman M
FAU - Bowes, John
AU  - Bowes J
FAU - Martin, Paul
AU  - Martin P
FAU - Comeau, Mary E
AU  - Comeau ME
FAU - Sajuthi, Satria
AU  - Sajuthi S
FAU - Andrews, Robert
AU  - Andrews R
FAU - Brown, Milton
AU  - Brown M
FAU - Chen, Wei-Min
AU  - Chen WM
FAU - Concannon, Patrick
AU  - Concannon P
FAU - Deloukas, Panos
AU  - Deloukas P
FAU - Edkins, Sarah
AU  - Edkins S
FAU - Eyre, Stephen
AU  - Eyre S
FAU - Gaffney, Patrick M
AU  - Gaffney PM
FAU - Guthery, Stephen L
AU  - Guthery SL
FAU - Guthridge, Joel M
AU  - Guthridge JM
FAU - Hunt, Sarah E
AU  - Hunt SE
FAU - James, Judith A
AU  - James JA
FAU - Keddache, Mehdi
AU  - Keddache M
FAU - Moser, Kathy L
AU  - Moser KL
FAU - Nigrovic, Peter A
AU  - Nigrovic PA
FAU - Onengut-Gumuscu, Suna
AU  - Onengut-Gumuscu S
FAU - Onslow, Mitchell L
AU  - Onslow ML
FAU - Rose, Carlos D
AU  - Rose CD
FAU - Rich, Stephen S
AU  - Rich SS
FAU - Steel, Kathryn J A
AU  - Steel KJ
FAU - Wakeland, Edward K
AU  - Wakeland EK
FAU - Wallace, Carol A
AU  - Wallace CA
FAU - Wedderburn, Lucy R
AU  - Wedderburn LR
FAU - Woo, Patricia
AU  - Woo P
CN  - Boston Children's JIA Registry
CN  - British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group
CN  - Childhood Arthritis Prospective Study (CAPS)
CN  - Childhood Arthritis Response to Medication Study (CHARMS)
CN  - German Society for Pediatric Rheumatology (GKJR)
CN  - JIA Gene Expression Study
CN  - NIAMS JIA Genetic Registry
CN  - TREAT Study
CN  - United Kingdom Juvenile Idiopathic Arthritis Genetics Consortium (UKJIAGC)
FAU - Bohnsack, John F
AU  - Bohnsack JF
FAU - Haas, Johannes Peter
AU  - Haas JP
FAU - Glass, David N
AU  - Glass DN
FAU - Langefeld, Carl D
AU  - Langefeld CD
FAU - Thomson, Wendy
AU  - Thomson W
FAU - Thompson, Susan D
AU  - Thompson SD
LA  - eng
GR  - R01-AR-060893/AR/NIAMS NIH HHS/United States
GR  - P01-AR-048929/AR/NIAMS NIH HHS/United States
GR  - P30 AR053483/AR/NIAMS NIH HHS/United States
GR  - R01 AR060893/AR/NIAMS NIH HHS/United States
GR  - U01 DK062432/DK/NIDDK NIH HHS/United States
GR  - 17552/ARC_/Arthritis Research UK/United Kingdom
GR  - R01-AR-057106/AR/NIAMS NIH HHS/United States
GR  - U01 DK062422/DK/NIDDK NIH HHS/United States
GR  - P01 AR048929/AR/NIAMS NIH HHS/United States
GR  - DK062431/DK/NIDDK NIH HHS/United States
GR  - N01AR42272/AR/NIAMS NIH HHS/United States
GR  - 17287/VAC_/Versus Arthritis/United Kingdom
GR  - N01AR-62277/AR/NIAMS NIH HHS/United States
GR  - U19-AI-082714/AI/NIAID NIH HHS/United States
GR  - P30-GM-103510/GM/NIGMS NIH HHS/United States
GR  - R01 AR057106/AR/NIAMS NIH HHS/United States
GR  - K23-AR-50177/AR/NIAMS NIH HHS/United States
GR  - N01AR62277/AR/NIAMS NIH HHS/United States
GR  - RC1-AR-058587/AR/NIAMS NIH HHS/United States
GR  - RC1 AR058587/AR/NIAMS NIH HHS/United States
GR  - U19 AI082714/AI/NIAID NIH HHS/United States
GR  - P30 GM103510/GM/NIGMS NIH HHS/United States
GR  - DK062422/DK/NIDDK NIH HHS/United States
GR  - RC2AR059092/AR/NIAMS NIH HHS/United States
GR  - U01 DK062413/DK/NIDDK NIH HHS/United States
GR  - RC2 AR059092/AR/NIAMS NIH HHS/United States
GR  - DK062423/DK/NIDDK NIH HHS/United States
GR  - U01 DK062429/DK/NIDDK NIH HHS/United States
GR  - 068545/Z/01/WT_/Wellcome Trust/United Kingdom
GR  - K23 AR050177/AR/NIAMS NIH HHS/United States
GR  - U01 DK062418/DK/NIDDK NIH HHS/United States
GR  - DK062420/DK/NIDDK NIH HHS/United States
GR  - G0000934/MRC_/Medical Research Council/United Kingdom
GR  - U01 DK062423/DK/NIDDK NIH HHS/United States
GR  - 17287/ARC_/Arthritis Research UK/United Kingdom
GR  - UL1 TR000077/TR/NCATS NIH HHS/United States
GR  - DK062429/DK/NIDDK NIH HHS/United States
GR  - P30-AR-053483/AR/NIAMS NIH HHS/United States
GR  - P30-AR-473639/AR/NIAMS NIH HHS/United States
GR  - U01 AI067150/AI/NIAID NIH HHS/United States
GR  - U01-AI-067150S1/AI/NIAID NIH HHS/United States
GR  - N01-AR-42272/AR/NIAMS NIH HHS/United States
GR  - P30 AR047363/AR/NIAMS NIH HHS/United States
GR  - DK062432/DK/NIDDK NIH HHS/United States
GR  - DK062413/DK/NIDDK NIH HHS/United States
GR  - U01 DK062420/DK/NIDDK NIH HHS/United States
GR  - U01 DK062431/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130421
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Interleukins)
RN  - 0 (Receptors, CCR)
RN  - 0 (Receptors, Interleukin)
SB  - IM
CIN - Nat Rev Rheumatol. 2013 Jun;9(6):320. PMID: 23649212
MH  - Adult
MH  - Arthritis, Juvenile/*genetics/immunology
MH  - Case-Control Studies
MH  - Child
MH  - Chromosome Mapping
MH  - Gene Frequency
MH  - Genetic Loci
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Humans
MH  - Interleukins/genetics
MH  - Linkage Disequilibrium
MH  - Molecular Sequence Annotation
MH  - Polymorphism, Single Nucleotide
MH  - Receptors, CCR/genetics
MH  - Receptors, Interleukin/genetics
MH  - Risk Factors
PMC - PMC3673707
MID - NIHMS474897
EDAT- 2013/04/23 06:00
MHDA- 2013/08/03 06:00
PMCR- 2013/12/01
CRDT- 2013/04/23 06:00
PHST- 2012/08/23 00:00 [received]
PHST- 2013/03/25 00:00 [accepted]
PHST- 2013/04/23 06:00 [entrez]
PHST- 2013/04/23 06:00 [pubmed]
PHST- 2013/08/03 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - ng.2614 [pii]
AID - 10.1038/ng.2614 [doi]
PST - ppublish
SO  - Nat Genet. 2013 Jun;45(6):664-9. doi: 10.1038/ng.2614. Epub 2013 Apr 21.