Osteoarthritis year 2013 in review: genetics and genomics

Progress in genetic research has delivered important highlights in the last year. One of the widest impact is the publication of the Encyclopedia of DNA Elements (ENCODE) project showing the impressive complexity of the human genome and providing information useful for all areas of genetics. More specific of osteoarthritis (OA) has been the incorporation of DOT1-like, histone H3 methyltransferase (DOT1L) to the list of 11 OA loci with genome-wide significant association, the demonstration of significant overlap between OA genetics and height or body mass index (BMI) genetics, and the tentative prioritization of HMG-box transcription factor 1 (HBP1) in the 7q22 locus based on functional analysis. In addition, the first large scale analysis of DNA methylation has found modest differences between OA and normal cartilage, but has identified a subgroup of OA patients with a very differentiated phenotype. The role of DNA methylation in regulation of NOS2, SOX9, MMP13 and IL1B has been further clarified. MicroRNA expression studies in turn have shown some replication of differences between OA and control cartilage from previous profiling studies and have identified potential regulators of TGFβ signaling and of IL1β effects. In addition, non-coding RNAs showed promising results as serum biomarkers of cartilage damage. Gene expression microarray studies have found important differences between studies of hip or knee OA that reinforce the idea of joint specificity in OA. Expression differences between articular cartilage and other types of cartilage highlighted the WNT pathway whose regulation is proposed as critical for maintaining the articular cartilage phenotype. Many of these results need confirmation but they signal the exciting progress that is taking place in all areas of OA genetics, indicate questions requiring more study and augur further interesting discoveries.