Genetics and epigenetics of osteoarthritis

Maturitas. 2012 Mar;71(3):200-4. doi: 10.1016/j.maturitas.2011.12.001. Epub 2011 Dec 29.


Osteoarthritis (OA) is a common age-related disease that affects the tissues of the synovial joint, leading to loss of function and pain. It impacts on both patient morbidity and mortality. It is a complex, polygenic disease that lacks any large-effect susceptibility loci. Instead, OA susceptibility alleles individually contribute only modestly to the overall disease risk, making their identification challenging. Despite this, breakthroughs have occurred with compelling associations so far reported to polymorphisms within the genes GDF5 and MCF2L and to the genomic region 7q22. The latter two have emerged from genome-wide association scans, which are likely to yield more hits in the near future. As for many complex diseases, it is now apparent that epigenetic effects are also important mediators of disease biology, with DNA methylation, histone modifications and non-coding RNAs all having a role. At present, much of the epigenetic focus has been on cartilage, the tissue at the center of the OA disease process. If we are to get close to a qualitative and quantitative understanding of the impact of epigenetics on OA, then in future the other tissues of the joint will also need to be investigated. One of the more exciting insights to have emerged recently is the fact that epigenetic effects can impact on OA genetic effects and this may be a particularly fruitful avenue for integrating both as we move toward a clearer understanding of the pathophysiology of this intriguing disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chromosomes, Human, Pair 7 / genetics
  • DNA Methylation / genetics
  • Epigenesis, Genetic*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Growth Differentiation Factor 5 / genetics
  • Guanine Nucleotide Exchange Factors / genetics
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Male
  • Multifactorial Inheritance
  • Osteoarthritis / genetics*
  • Polymorphism, Genetic
  • RNA, Untranslated / genetics
  • Rho Guanine Nucleotide Exchange Factors


  • GDF5 protein, human
  • Growth Differentiation Factor 5
  • Guanine Nucleotide Exchange Factors
  • Histones
  • MCF2L protein, human
  • RNA, Untranslated
  • Rho Guanine Nucleotide Exchange Factors