Computational modelling predicted that rs6060369 occupied and disrupted the TF binding site for pituitary homeobox-1 (PITX1), a critical TF for knee development [73], which was functionally validated using ChIP-Seq, supportive of the enhanceropathy model depicted in Fig. 1A. This study was the first to demonstrate that an osteoarthritis-associated enhancer variant controlling early development of the human knee joint can predispose humans to osteoarthritis in later, post-reproductive life: a phenomenon known as antagonistic pleiotropy [74]. The gene discussed is TF; the disease is osteoarthritis.