The allelic imbalance of the DIO2 mRNA transcript, with the OA risk allele 'C' of rs225014 more abundant than the wild-type 'T' allele in heterozygote carriers provides a possible mechanism by which genetic variation at DIO2 confers OA risk.
Allele-sharing methods were applied to the symptomatic osteoarthritis GARP study where taking into account the family-history increased considerably the evidence of linkage in the region of the DIO2 susceptibility locus.
Genetic association studies have identified a few consistent osteoarthritis susceptibility genes (FRZB, GDF5, and DIO2) that replicate across different populations.
Our findings show how genetic variation at DIO2 could confer risk to OA and raised the possibility that counteracting thyroid signalling may be a novel therapeutic approach.