In addition, PheWAS analysis of these key TFs from regulatory networks showed ESR1, ISL1, RUNX2, SIX1 and SMAD3 were associated with human skeletal phenotypes, including bone mineral density, height, osteoarthritis of hip or knee; FOXO1, MEF2C and TRP53 were associated with human metabolic phenotypes, including leg fat ratio, fat mass or percentage (Figure S4). The gene discussed is RUNX2; the disease is osteoarthritis.