Decoding the genomic basis of osteoarthritis
Steinberg, J.; Southam, L.; Butterfield, N. C.; Roumeliotis, T. I.; Fontalis, A.; Clark, M. J.; Jayasuriya, R. L.; Swift, D.; Shah, K. M.; Curry, K. F.; Brooks, R. A.; McCaskie, A. W.; Lelliott, C. J.; Choudhary, J. S.; Bassett, J. D.; Williams, G. R.; Wilkinson, J. M.; Zeggini, E.
Show abstract
Osteoarthritis causes pain and functional disability for a quarter of a billion people worldwide, with no disease-stratifying tools nor modifying therapy. Here, we use primary cartilage and synovium from osteoarthritis patients to construct a molecular quantitative trait locus map of gene expression and protein abundance. By integrating data across omics levels, we identify likely effector genes for osteoarthritis-associated genetic signals. We detect pronounced molecular differences between macroscopically intact and highly degenerated cartilage. We identify molecularly-defined patient subgroups that correlate with clinical characteristics, stratifying patients on the basis of their molecular profile. We construct and validate a 7-gene classifier that reproducibly distinguishes between these disease subtypes, and identify potentially actionable compounds for disease modification and drug repurposing.
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