Document Detail


Susceptibility to childhood-onset rheumatoid arthritis: investigation of a weighted genetic risk score that integrates cumulative effects of variants at five genetic loci.
MedLine Citation:
PMID:  23450725     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Children with childhood-onset rheumatoid arthritis (RA) include those with rheumatoid factor or anti-citrullinated protein antibody-positive juvenile idiopathic arthritis. To test the hypothesis that adult-onset RA-associated variants are also associated with childhood-onset RA, we investigated RA-associated variants at 5 loci in a cohort of patients with childhood-onset RA. We also assessed the cumulative association of these variants in susceptibility to childhood-onset RA using a weighted genetic risk score (wGRS).
METHODS: A total of 155 children with childhood-onset RA and 684 healthy controls were genotyped for 5 variants in the PTPN22, TRAF1/C5, STAT4, and TNFAIP3 loci. High-resolution HLA-DRB1 genotypes were available for 149 cases and 373 controls. We tested each locus for association with childhood-onset RA via logistic regression. We also computed a wGRS for each subject, with weights based on the natural log of the published odds ratios (ORs) for the alleles investigated, and used logistic regression to test the wGRS for association with childhood-onset RA.
RESULTS: Childhood-onset RA was associated with TNFAIP3 rs10499194 (OR 0.60 [95% confidence interval 0.44-0.83]), PTPN22 rs2476601 (OR 1.61 [95% confidence interval 1.11-2.31]), and STAT4 rs7574865 (OR 1.41 [95% confidence interval 1.06-1.87]) variants. The wGRS was significantly different between cases and controls (P < 2 × 10(-16) ). Individuals in the third to fifth quintiles of wGRS had a significantly increased disease risk compared to baseline (individuals in the first quintile). Higher wGRS was associated with increased risk of childhood-onset RA, especially among males.
CONCLUSION: The magnitude and direction of the association between TNFAIP3, STAT4, and PTPN22 variants and childhood-onset RA are similar to those observed in RA, suggesting that adult-onset RA and childhood-onset RA share common genetic risk factors. Using a wGRS, we have demonstrated the cumulative association of RA-associated variants with susceptibility to childhood-onset RA.
Authors:
Sampath Prahalad; Karen N Conneely; Yunxuan Jiang; Marc Sudman; Carol A Wallace; Milton R Brown; Lori A Ponder; Mina Rohani-Pichavant; Michael E Zwick; David J Cutler; Sheila T Angeles-Han; Larry B Vogler; Christine Kennedy; Kelly Rouster-Stevens; Carol A Wise; Marilynn Punaro; Ann M Reed; Elizabeth D Mellins; John F Bohnsack; David N Glass; Susan D Thompson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-03     Completed Date:  2013-08-13     Revised Date:  2013-08-22    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1663-7     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
Affiliation:
Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Age Factors
Arthritis, Rheumatoid / genetics*
Child
Female
Genetic Loci
Genetic Predisposition to Disease*
Genotype
Humans
Male
Risk Assessment
Grant Support
ID/Acronym/Agency:
N01-AR-42272/AR/NIAMS NIH HHS; P01 AR048929/AR/NIAMS NIH HHS; P01-AR-048929/AR/NIAMS NIH HHS; P30 AR047363/AR/NIAMS NIH HHS; P30-AR-047363/AR/NIAMS NIH HHS; R01 AR060893/AR/NIAMS NIH HHS; R01 AR061297/AR/NIAMS NIH HHS; R01-AR-049762/AR/NIAMS NIH HHS; R01-AR-060893/AR/NIAMS NIH HHS; R21 AI075254/AI/NIAID NIH HHS; R21-AI-075254/AI/NIAID NIH HHS; RC1 AR058587/AR/NIAMS NIH HHS; RC1-AR-058587/AR/NIAMS NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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