Genetics and Epigenetics in Obesity: What Do We Know so Far?

Abstract

Purpose of Review Enormous progress has been made in understanding the genetic architecture of obesity and the correlation of epigenetic marks with obesity and related traits. This review highlights current research and its challenges in genetics and epigenetics of obesity. Recent Findings Recent progress in genetics of polygenic traits, particularly represented by genome-wide association studies, led to the discovery of hundreds of genetic variants associated with obesity, which allows constructing polygenic risk scores (PGS). In addition, epigenome-wide association studies helped identifying novel targets and methylation sites being important in the pathophysiology of obesity and which are essential for the generation of methylation risk scores (MRS). Despite their great potential for predicting the individual risk for obesity, the use of PGS and MRS remains challenging. Summary Future research will likely discover more loci being involved in obesity, which will contribute to better understanding of the complex etiology of human obesity. The ultimate goal from a clinical perspective will be generating highly robust and accurate prediction scores allowing clinicians to predict obesity as well as individual responses to body weight loss-specific life-style interventions.

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“…Obesity is a complex disorder with a multifaceted etiology influenced by a complex interplay of genetic, environmental, and lifestyle factors. While genetics lay the groundwork for susceptibility, environmental influences, particularly diet and physical activity, and epigenetic modifications play pivotal roles in the manifestation of obesity ( 1 , 2 ). Over the past decade, research has unveiled the critical role of the gut microbiome in the development of obesity and its contribution to the reversal of metabolic disorders in general ( 3–6 ), placing the gut microbiome at the center of new strategies to prevent, treat and reverse obesity.…”