Epigenomics And Human Obesity

Obesity has become one of the most urgent public health problems globally with the steepest increases in prevalence reported among socioeconomically disadvantaged groups. In resource-rich settings, many of these disadvantaged are also ethnic minorities. In adults, obesity is associated with sizable reductions in life expectancy and quality of life, but it also is a consistent risk factor for comorbid conditions that include type 2 diabetes, cardiovascular diseases, and multiple forms of cancer and is fueling the increase in chronic liver diseases. In children, obesity is associated with school absenteeism and lower educational attainment, and as adults, lower income and occupational productivity, and thus a higher likelihood of poverty. Although animal and in vitro evidence supports that epigenetic dysregulation may be causally related to obesity, the affected pathways remain obscure. This chapter summarizes obesity-related human data on CpG methylation of DNA, the most studied epigenetic mechanism in humans, in the context of causal inference. Particular focus is given to epigenetic marks established before tissue-specification, including those regulating genomically imprinted genes, as well as metastable epialleles, and the identification of these regions in adults and children using methods made possible by recent advances in technologies for genome-scale methylation microarrays and methyl-sequencing. Still limited, however, are data on the temporal stability of regions identified thus far, and data on obesity-related sequence regions in populations including the socioeconomically disadvantaged and ethnic minorities. To enhance causal inference, we therefore conclude with a call for studies that evaluate these issues, examining the temporal stability and association with socioeconomic and ethnic differences for obesity-associated DNA methylation marks identified thus far.