Osteoarthritis year in review 2019: genetics, genomics and epigenetics

Although osteoarthritis (OA) aetiology is complex, genetic, genomic and epigenetic studies published within the last decade have advanced our understanding of the molecular processes underlying this common musculoskeletal disease. The purpose of this narrative review is to highlight the key research articles within the OA genetics, genomics and epigenetics fields that were published between April 2018 and April 2019. The review focuses on the identification of new OA genetic risk loci, genomics techniques that have been used for the first time in human cartilage and new publicly available databases, and datasets that will aid OA functional studies. Fifty-six new OA susceptibility loci were identified by two large scale genome wide association study meta-analyses, increasing the number of genome-wide significant risk loci to 90. OA risk variants are enriched near genes involved in skeletal development and morphology, and show genetic overlap with height, hip shape, bone area and developmental dysplasia of the hip. Several functional studies of OA loci were published, including a genome-wide analysis of genetic variation on cartilage gene expression. A specialised data portal for exploring cross-species skeletal transcriptomic datasets has been developed, and the first use of cartilage single cell RNAseq analysis reported. This year also saw the systematic identification of all microRNAs, long non-coding RNAs and circular RNAs expressed in human OA cartilage. Putative transcriptional regulatory regions have been mapped in human chondrocytes genome-wide, providing a dataset that will facilitate the prioritisation and characterisation of OA genetic and epigenetic loci. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.