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NIH Research Festival

September 16 – 18, 2015

Gene-Based Association Testing and Pathway Analysis of Systemic Juvenile Idiopathic Arthritis Implicates Cadherin and Wnt Signaling Pathways

Friday, September 18, 2015 – Poster Session IV
12:00 – 1:30 p.m.

FAES Terrace

NIAMS

GEN-2

Authors

  • VL Arthur
  • MJ Ombrello
  • on behalf of INCHARGE Consortium

Abstract

Systemic juvenile idiopathic arthritis (sJIA) is a rare, life-threatening inflammatory disease of unknown etiology. To study the genetics of this rare disease, we established international collaboration and assembled the largest sJIA case-control collection, to date. Single nucleotide polymorphism (SNP) genotypes were determined in 982 children with sJIA and 431 healthy subjects. Data were merged with in silico SNP data from 7,579 additional healthy subjects and were stratified by country of origin. SNP imputation and association testing were performed separately in 9 case-control strata, and associations were meta-analyzed. Gene-based associations were determined with VEGAS2, GATES, and BIOFILTER using SNPs with pmeta3000 SNPs with at least suggestive evidence of association with sJIA (pmeta1 method. Pathway-based analyses identified two pathways (cadherin and Wnt signaling pathways) that were consistently enriched with sJIA-associated genes under diverse testing conditions (PANTHER overrepresentation test pminimum: cadherin 3E-13; Wnt 2E-10). This study is the first to suggest that the cadherin signaling pathway and Wnt signaling pathway are involved in the pathophysiology of sJIA. Both of these pathways are involved in cell adhesion and migration, as well as in regulation of epithelial-mesenchymal transition (EMT), a critical element of wound healing through which mesenchymal stem cells are produced from epithelial cells. These findings warrant further investigation of the cadherin and Wnt signaling pathways in sJIA.

Scientific Focus Area: Genetics and Genomics

This page was last updated on Friday, March 26, 2021

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