Cindy Boer

General Discussion | 267 6 ▲ Figure 5: the multiple omics layers and interactions leading to osteoarthritis. Schematically several omics- layers are represented. The exposome (environment) influences/interacts with all omics, except for the genome. The genome does underly the epigenome/transcriptome and proteome directly, but only indirect the other omics. Black dots and lines represent possible pathological pathways and inter- actions within and between omics-layers resulting in osteoarthritis pathology. other complex diseases similar success of ever larger GWAS have been reported, with some reaching sample sizes of over 1 million[48, 49]. With the formation and ongoing efforts of the Genetics of Osteoarthritis (GO) consortium, such large sample sizes are also becoming possible for osteoarthritis GWAS. Although the first success has been made by the GO consortium, several issues need to be addressed. Much of the herit- ability (~94-79%) of osteoarthritis remains unexplained, although the low predicted heritability (8%-22%) seen in the GO consortium could be large explained by bias/ heterogeneity of the used osteoarthritis phenotypes. In general ( Table 1 ) this “miss-