Genetics of osteoarthritis

Curr Opin Rheumatol. 2011 Sep;23(5):479-83. doi: 10.1097/BOR.0b013e3283493ff0.


Purpose of review: A number of reasonably powered osteoarthritis genome-wide association scans are now in the final phases of their analysis, leaving us all with baited breath. This review highlights some of the osteoarthritis signals and subsequent insights that have emerged from the candidate studies and smaller scale scans that have preceded these more powered studies, and which could therefore be considered as appetizers to the hopeful treats to follow.

Recent findings: If one applies the strict criteria of genome-wide significance thresholds, only two current signals pass muster: GDF5 and 7p22. If one relaxes slightly, other signals emerge, such as DIO2, SMAD3 and ASPN. After these, however, we enter the realm where faith takes precedence.

Summary: The search for osteoarthritis susceptibility loci has not been as successful as many had anticipated. This reflects many factors, including the heterogeneous nature of the disease, the tendency to use less severe phenotypes in genetic searches and the reliance on underpowered studies. We do, however, have some successes and in the very near future others will emerge from the more powered scans. Hopefully, combining the current with the new will help our attempts to understand the cause of this complex, common arthritis.

Publication types

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

MeSH terms

  • Animals
  • Chromosomes, Human, Pair 7 / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Growth Differentiation Factor 5 / genetics
  • Humans
  • Japan
  • Linkage Disequilibrium
  • Mice
  • Netherlands
  • Osteoarthritis / genetics*
  • Polymorphism, Single Nucleotide
  • Smad3 Protein / genetics
  • Transforming Growth Factor beta / genetics
  • United Kingdom


  • GDF5 protein, human
  • Growth Differentiation Factor 5
  • SMAD3 protein, human
  • Smad3 Protein
  • Transforming Growth Factor beta