FXR is well known to play a key role in age-associated changes in the liver transcriptome, as well development of liver disease and HCC 38,39, suggesting a combined effect of epigenomic reprogramming (Figure 7d) and altered transcription factor activity (Suppl Figure 7c) as potential drivers for the increased risk for liver tumors associated with this high risk endotype. The gene discussed is NR1H4; the disease is hepatocellular carcinoma.