Genome-wide association studies (GWAS) and candidate gene studies have informed our understanding of factors contributing to the well-recognized inter-individual variation in progression and outcomes of alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). We discuss the mounting evidence for shared modifiers and common pathophysiological processes that contribute to development of both diseases. We discuss the functions of proteins encoded by risk variants of genes including PNPLA3 and TM6SF2, as well as epigenetic factors that contribute to the pathogenesis of ALD and NAFLD.