Genome-Wide DNA and Histone Modification Studies in Metabolic Disease

Summary, in English

The last decade has witnessed a revolution in genetic technology, where genome-wide analyses, covering the majority of genetic variation, were thought to explain disease-causing mechanisms in common metabolic disorders. However, these genetic data only explain a modest proportion of the estimated heritability of type 2 diabetes and obesity and hence suggest a potential role for epigenetic variation in the etiology of metabolic disease. Indeed, recent genome-wide epigenetic studies have identified altered DNA methylation patterns in human pancreatic islets, adipose tissue, skeletal muscle, and blood from subjects with type 2 diabetes compared with normal subjects. Also, measures of obesity, such as increased body mass index (BMI), have been associated with epigenetic modifications in humans. It should also be noted that environmental risk factors for metabolic disease, for example, energy-rich diets, physical inactivity, and aging have been found to alter the epigenetic pattern genome-wide and in candidate genes for type 2 diabetes and obesity in human tissues. Additionally, interactions between genetic and epigenetic variations seem to contribute to the risk for metabolic disease. Together, genome-wide epigenetic studies highlight the importance of altered DNA methylation and histone modifications in the pathogenesis of metabolic disease. This chapter aims at summarizing current knowledge in the field of metabolic disease and genome-wide epigenetic analyses in humans.