TNFRSF25 and bone disorder: With specific regard to disorders of bone, initial genetic studies suggested that DR‐3 gene duplication 44 and a mutation predicted to destabilize DR‐3 (45) were linked to development of RA, while synovial cells from RA patients exhibited a hypermethylated DR‐3 gene suggestive of activation 46; however, genome‐wide association studies have had less success with supporting this connection.