The genetics of NAFLD

Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):645-55. doi: 10.1038/nrgastro.2013.182. Epub 2013 Sep 24.


NAFLD is a disease spectrum ranging from simple steatosis, through steatohepatitis to fibrosis and, ultimately, cirrhosis. This condition is characterized by considerable interpatient variability in terms of severity and rate of progression: although a substantial proportion of the population is at risk of progressive disease, only a minority experience associated morbidity. As such, NAFLD is best considered a complex disease trait resulting from environmental exposures acting on a susceptible polygenic background and comprising multiple independent modifiers. Much ongoing research is focused on identifying the genetic factors that contribute to NAFLD pathogenesis. This Review describes the current status of the field, discussing specific genetic and epigenetic modifiers, including the mechanisms through which genes identified by genome-wide association studies, including PNPLA3, influence disease progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Disease Progression*
  • Epigenomics*
  • Fatty Liver / genetics*
  • Fatty Liver / physiopathology
  • Genome-Wide Association Study
  • Humans
  • Lipase / genetics
  • Lipase / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Non-alcoholic Fatty Liver Disease
  • Severity of Illness Index


  • Membrane Proteins
  • Lipase
  • adiponutrin, human