AsianScientist (Dec. 31, 2013) – The largest international study to date into the genetic basis of rheumatoid arthritis has shed light on the biology of how existing drugs target the disease.
It is also the first study to provide evidence that large-scale genetic studies can assist in the identification of new drugs for complex disorders such as rheumatoid arthritis.
Results of the study, led by Dr. Robert M. Plenge from the Harvard Medical School and the Broad Institute in the US and Dr. Yukinori Okada from the RIKEN Center for Integrative Medical Sciences in Japan, together with colleagues from 70 institutions worldwide, are published in the journal Nature.
Rheumatoid arthritis is an autoimmune disease leading to inflammation of the joints and affecting 0.5-1 percent of adults in the developed world. The disease is thought to be caused by a complex combination of genetic and environmental factors and several genes have been shown to be associated with the disease. However, most of the findings were based on single population studies, and no large-scale trans-ethnic study had been carried out to date.
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 ten million genetic variants called single nucleotide polymorphism (SNPs).
They identified 42 new regions in the genome (loci) that are associated with rheumatoid arthritis, bringing the total number of known rheumatoid arthritis loci to 101. By conducting bioinformatics studies integrating existing datasets with this new information, the researchers were able to pinpoint 98 genes in these 101 loci that could potentially contribute to the onset of rheumatoid arthritis.
The researchers integrated their findings with existing drug databases and demonstrated that these genes possess many overlapping regions with the genes targeted by approved rheumatoid arthritis drugs – although this wasn’t known when the drugs were developed.
The study also revealed that there is significant overlap between the genes involved in rheumatoid arthritis, human primary immunodeficiency disorders and blood cancers. Hence, existing drugs used to treat cancer, such as CDK4/6 inhibitors, could potentially be used as therapy for the disease.
The article can be found at: Okada Y et al. (2013) Genetics of rheumatoid arthritis contributes to biology and drug discovery.
Source: RIKEN; Photo: Matt Erasmus/Flickr/CC.
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