Additional Genes Linked to Juvenile Arthritis

The number of confirmed genes linked to juvenile idiopathic arthritis (JIA) has increased from the original three to 17 or possible more.

These additional genes will help clarify how JIA fits into the spectrum of autoimmune disorders and may reveal even more genes and pathways that will help identify potential treatment targets.

An international team of scientists has analyzed 2,816 JIA cases recruited from more than 40 pediatric rheumatology clinics. It was the largest collaborative patient population of JIA to date, including patient DNA samples from across the United States of America, Germany, and the United Kingdom. The USA cohorts comprised 1,596 oligoarticular and rheumatoid factor (RF)-negative polyarticular JIA cases and 4,048 US controls. Less than half of these cases have already been included in a genome-wide association study (GWAS).

The international team led by scientists from the Cincinnati Children's Hospital Medical Center (OH, USA; www.cincinnatichildrens.org) used what is known as the Immunochip, a custom Infinium array (Illumina; San Diego, CA, USA). The Immunochip measures variation in the genes (DNA) coding for components of the immune system for all the JIA patients in the study. Those findings were compared to the DNA of 13,000 healthy controls to look for genetic differences. The single nucleotide polymorphisms (SNP) genotype imputations were computed across the regions of the Immunochip.

The analyses reconfirmed JIA's connection to the original three genes, identified a link to the 14 new genes, and pointed to the possibility that another 11 genetic regions may be implicated. The scientists stressed that their work continues in order to identify additional genetic links and also began conducting functional studies to pinpoint disease processes. The entire Immunochip content, the human leukocyte antigen (HLA) region and the top 27 loci explain an estimated 18%, 13%, and 6% of risk of JIA, respectively. These estimates also suggest that there must be other regions of the genome harboring additional JIA risk loci.

Susan D. Thompson, PhD, a senior author of the study said, “These findings will help us understand how the long suspected genetic contributions to JIA are driving the disease process, with the ultimate goal being earlier and improved diagnosis and treatment.” The other confirmed loci were the protein tyrosine phosphatase, nonreceptor type 22 (lymphoid), (PTPN22), and the tyrosine-protein phosphatase nonreceptor type 2 enzyme (PTPN2). The study was published on April 21, 2013, in the journal Nature Genetics.


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Cincinnati Children's Hospital Medical Center
Illumina