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Dec 26, 2013

Huge Gene Study Boosts New Drug Hopes for Rheumatoid Arthritis

Huge Gene Study Boosts New Drug Hopes for Rheumatoid Arthritis

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  • Researchers say that the results of the largest international study to date into the genetic basis of rheumatoid arthritis has increased our knowledge of the biology of the disease and provided evidence that large-scale genetic studies can assist in the identification of new drugs for complex disorders such as rheumatoid arthritis. The study (“Genetics of rheumatoid arthritis contributes to biology and drug discovery”), conducted by Robert M. Plenge, M.D., Ph.D., from the Harvard Medical School and the Broad Institute, and Yukinori Okada, M.D., Ph.D, from the Riken Center for Integrative Medical Sciences, collaborating with colleagues from 70 institutions worldwide, is published in Nature.

    Genome-wide association studies are a method employed by scientists to identify the genes contributing to human disease. The current Nature study reportedly is the first to demonstrate that integrating the information provided by genome-wide association studies with existing datasets of genomic and biological information, such as drug targets, can assist in the discovery of drugs to cure human disease.

    The international team performed a genome-wide association study meta-analysis on a total of over 100,000 subjects of European and Asian descent (29,880 rheumatoid arthritis patients and 73,758 controls) by analyzing around 10 million single nucleotide polymorphism. They identified 42 new loci that are associated with rheumatoid arthritis, bringing the total number of known rheumatoid arthritis loci to 101.

    “We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses—as well as novel methods based on genetic overlap with human primary immunodeficiency, hematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci,” wrote the investigators. “We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.”

    The bioinformatics study also reveals that there is significant overlap between the genes involved in rheumatoid arthritis, human primary immunodeficiency disorders, and blood cancers.

    “This study sheds light on the fundamental genes, pathways and cell types that contribute to the onset of rheumatoid arthritis and provides evidence that the genetics of rheumatoid arthritis can provide important information for drug discovery,” conclude the authors.



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