Decoding the genomic basis of osteoarthritis
Natalie C Butterfield,
Theodoros I. Roumeliotis,
Matthew J Clark,
Raveen L. Jayasuriya,
Karan M. Shah,
Katherine F Curry,
Roger A. Brooks,
Andrew W. McCaskie,
Christopher J Lelliott,
Jyoti S. Choudhary,
JH Duncan Bassett,
Graham R Williams,
J Mark Wilkinson,
Posted 12 Nov 2019
bioRxiv DOI: 10.1101/835850
Posted 12 Nov 2019
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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