Researchers at Massachusetts General Hospital found that patients with nonalcoholic fatty liver disease (NAFLD) who carry an allele of the PNPLA3 gene have an increased risk of developing advanced disease, including nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. A second study supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) validates these findings and further concludes that in pediatric patients, the same allele is associated with earlier disease presentation. Both studies are available in the September issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD). NAFLD is the most common cause of chronic liver disease and afflicts an estimated 20%-30% of the general population and 67%-75% of the obese population. The precise mechanism responsible for the development of the NASH phenotype is yet to be clarified. Genome-wide association (GWA) studies are an important initial step in the identification of these genetic factors because they evaluate the genotypic-phenotypic association in large population-based cohorts and have identified susceptibility loci in numerous diseases.