PNPLA3 interacts strongly with insulin resistance to drive hepatic steatosis, and a combination of the PNPLA3 risk allele, insulin resistance, and their interaction explained 8% of the variation in hepatic steatosis in nondiabetic individuals, suggesting that many individuals at high risk of hepatic steatosis are not currently being treated (67). This evidence concerns the gene PNPLA3 and fatty liver disease.