An epigenome-wide view of osteoarthritis in primary tissues

• DOI: 10.1016/j.ajhg.2022.05.010
• Publication Date: 2022-06-08T14:32:29Z
• Authors: Peter Kreitmaier; Matthew Suderman; Lorraine Southam; Rodrigo Coutinho ...; Konstantinos Hatz...; Ingrid Meulenbelt; Julia Steinberg; Caroline L. Relton; J. Mark Wilkinson; Eleftheria Zeggini
• Keywords: Epigenome; Genome-wide Association Study

Osteoarthritis is a complex degenerative joint disease. Here, we investigate matched genotype and methylation profiles of primary chondrocytes from macroscopically intact (low-grade) degraded (high-grade) osteoarthritis cartilage synoviocytes collected 98 osteoarthritis-affected individuals undergoing knee replacement surgery. We perform an epigenome-wide association study degeneration report robustly replicating markers, which reveal etiologic mechanism linked to the migration epithelial cells. Using machine learning, derive models degeneration, validate with 82% accuracy in independent data. genome-wide quantitative trait locus (mQTL) map articular synovium identify 18 disease-grade-specific mQTLs cartilage. resolve GWAS loci through causal inference colocalization analyses decipher epigenetic mechanisms that mediate effect on disease risk. Together, our findings provide enhanced insights into underlying tissues.