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Many studies have estimated heritability of body mass index (BMI) and related variables, and they are consistent in finding moderate to high heritability. Genes central to energy balance tend to have low variability, presumably because of strong selection pressure. Even so, some have argued that mutations in a large number of genes may account for most human obesity and other common diseases. Substantial progress in finding rare variants has come with a focus on copy number variation (CNV). Whole genome association (WGA) studies have several advantages over whole genome linkage scans. Gene-environment interaction can play an important role in the development of obesity, although it should be born in mind that this may only complicate things further, as environmental response is itself heritable. Epigenetics are discussed in this chapter. WGA studies results have demonstrated that there are indeed common variants in genes that increase risk for obesity.