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.
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.