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Non-alcoholic fatty liver disease (NAFLD) is a complex and widely prevalent liver disorder, traditionally characterised by pathological changes ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) that can further progress to cirrhosis and hepatocellular carcinoma. Owing to the epidemics of obesity and metabolic syndrome, NAFLD is the most frequent liver disorder in the Western world. It is considered to be a multifactorial state, leading not only to liver related mortality but also to increased cardiovascular, type 2 diabetes mellitus and the overall mortality. The natural course of NAFLD is highly variable and is influenced by both environmental and genetic factors. Candidate gene and genome wide association studies together with other clinical data reveal the importance of genetic factors in susceptibility to NAFLD where polymorphisms in genes involved in the control of insulin resistance, lipid metabolism, inflammation and oxidative stress are linked to the progression of liver damage. To date, polymorphisms in PNPLPA3, the patatin-like phospholipase domain containing 3 gene, remain the most consistent genetic association with NAFLD while a number of other genetic polymorphisms have been associated with the disease in case–control studies. It is now necessary to explore the molecular mechanism underlying associations between gene variants and pathogenesis of various stages of NAFLD. Key Concepts NAFLD is a complex disease influenced by both genetic and environmental factors which interact to determine the disease phenotype and its progression. The pathogenesis of NAFLD remains poorly understood. It is under debate if the development of simple steatosis and NASH is the result of two or multiple hits, or whether it is a more complex network phenomenon. Susceptibility to and progression of NAFLD differ according to race, ethnicity, gender and lifestyle. Several SNPs in the human genome associate with susceptibility to and progression of NAFLD. The most consistently replicated genetic risk factor for NAFLD disease is the rs738409 polymorphism in the human PNPLA3, the patatin-like phospholipase domain containing gene 3, also called adiponutrin. Other SNPs in genes influencing lipid metabolism, insulin resistance, inflammation, oxidative stress, extracellular matrix synthesis, degradation, apoptosis, and so on associate with NAFLD; however, they require conformation before being formally associated with NAFLD stages. Keywords: non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH); hepatocellular carcinoma; genetics; single nucleotide polymorphism (SNP); genome wide association studies (GWAS); clinical studies