December 2010 Newsletter
Biomarkers Workshop Atlanta
On November 4 and 5 a group of 125 people from across the globe gathered in Atlanta for the 2nd OARSI Biomarkers workshop titled Genetics and Genomics: New Targets in OA..
Genetic studies in OA have so far provided us with a handful of robust genes / gene loci, such as GDF5, 7q22, DIO2, FRZB and more are expected as ongoing GWAS studies are completed.
- Functional studies are critical and functional genomic pipelines are necessary to discover the molecular pathway underlying OA etiology to facilitate the discovery of much needed new druggable targets.
- Current OA susceptibility genes are not providing additional risk predictions on top of the conventional risk factors such as age, gender and BMI. Focus should be on the elucidation of the underlying pathways.
Current large-scale consortia such as arcOGEN and TREAT~OA are converging towards a few robust new OA targets with genome wide significance (P < 10-8).
- We need additional (quantitative) phenotyping to allow genome wide analyses of OA endophenotypes such as biochemical markers or joint shape.
- A clearance house at the OARSI website is necessary to allow an overview of current available studies and data (upcoming GWA's of OAI samples as an example).
- A large part of the heritability remains unexplained; deep sequencing (whole genome, exome, RNA-seq) may provide a novel tool to uncover additional (rare) genetic variation that may fill-in some of the gap.
Additional potential genomic OA biomarkers
- Micro array expression profiles in blood may be an assessable new source of sensitive genomic biomarkers.
- Micro array expression profiles in cartilage have provided insight in to OA pathopysiology, however, the inaccessibility of the tissue limits their use as biomarkers of OA
- Epigenetic profiling of cartilage.
This workshop was the 2nd in a series of three, with the first focusing on conventional biochemical biomarkers and the third on imaging. What's clear thus far, is that an integration of all three forms of biomarker will be critical if we, as a research community, are going to be able to understand this complex disease and provide robust tools that assist in the development and subsequent trialing of new treatments. Genetic research is starting to provide us with novel insights but much still needs to be learnt. By the 3rd and final workshop, taking place in 2012, the hope is that more substantive steps will have been taken.