Author:
Steinberg Julia,Southam Lorraine,Butterfield Natalie C,Roumeliotis Theodoros I,Fontalis Andreas,Clark Matthew J,Jayasuriya Raveen L,Swift Diane,Shah Karan M,Curry Katherine F,Brooks Roger A,McCaskie Andrew W,Lelliott Christopher J.,Choudhary Jyoti S,Bassett JH Duncan,Williams Graham R,Wilkinson J Mark,Zeggini Eleftheria
Abstract
AbstractOsteoarthritis 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
10 articles.
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