Epigenetic risk mechanisms of osteoarthritis during human skeletal development
Dr Sarah Rice (Newcastle University)
SM2 Ada Lovelace Building
A Snapshot seminar hosted by the School of Physiology, Pharmacology and Neuroscience
Abstract: Increasing evidence is emerging to link age-associated complex musculoskeletal diseases, including OA, to developmental factors. Multiple studies have shown a functional role for DNA methylation in the genetic mechanisms of OA risk using articular cartilage samples taken from aged patients, yet knowledge of temporal changes to the methylome during human cartilage development is limited. We have recently quantified DNA methylation at ~700,000 individual CpGs across the epigenome of developing human articular cartilage in 72 samples ranging from 7-21 post-conception weeks. We identified significant changes in 8% of all CpGs, and >9400 developmental differentially methylated regions. We identified 26 loci at which OA genetic variants colocalise with methylation QTLs. Through integrating developmental and mature human chondrocyte datasets, we find evidence for functional effects exerted solely in development, or throughout the life course. This will have profound impacts on future approaches to translating genetic pathways for therapeutic intervention.