Cindy Boer

General Discussion | 271 6 could prevent or decrease joint pain and inflammation, possible therapeutic strategies include antibiotics, diet intervention, faecal transplants or even microbial metabolites [55, 56]. However, these therapies also affect the rest of the gastrointestinal microbi- ome. If the exact Streptococcus species or strain is known specific antibiotics, probiotics or introduction of competitor species could be used, without affecting the entire micro- biome composition. Thus, still quite some research is needed before the microbiome is truly part of the osteoarthritis risk factors and possible therapeutic targets. Post GWAS era: move to the clinic The increase in osteoarthritis genetic loci over the last decade has not only increased the understanding of osteoarthritis genetics, but also understanding of osteoarthritis pathology. Especially, translational research into GWAS results has demonstrated novel genes, pathways and mechanisms to be involved in osteoarthritis pathology. Some are now considered or in the development process for novel treatment strategies: MGP(os- teoarthritis in any joint, Vitamin K)( Chapter 3 )[21, 36] , TGFB1 (knee osteoarthritis, IN- VOSSA)[57] , CSTK (extracellular matrix turnover/inflammation inhibitor, CSTK inhibitor) [58] and FGF18(cartilage regeneration for knee osteoarthritis, Sprifermin)[59] . However, a true move from GWAS to clinical treatment has not (yet) been made for osteoarthri- tis, for this to happen considerable more functional follow-up and translational studies are needed. Particularly, bioinformatic investigation of omics, multi-omics and inte- grative omics is needed ( Figure 5 ). Although for osteoarthritis, some omics resources exist (cartilage and bone gene expression, methylation, histone markers , ATAC-seq), the data is scarce and is measured in few individuals or only in specific states (healthy or diseased). What is needed, is a large scale integrative multi-omics data resource: measuring multiple osteoarthritis relevant tissues, tissue states and omics-layers in one large group of individuals. Several biobanks and groups are working towards such a goal (UK-biobank, ROADMAP, ENCODE), albeit not specifically for osteoarthritis or os- teoarthritis relevant tissue. Imagine the possibilities of such an osteoarthritis specific resource, considering the immense value and insight the current limited osteoarthritis specific omics data have provided so far. Such a data resource will be invaluable for the identification of novel osteoarthritis associated genes, pathways and therapeutic development. Osteoarthritis associated SNVs could potentially also directly be used in a clin- ical setting. These SNVs could be used to create an individual level genetic risk score or polygenic risk score (PRS) for osteoarthritis. These scores reflect an individual’s genetic risk for developing a certain disease[60]. For osteoarthritis, currently 148 genomic loci