Obesity: Genetics

Abstract

Obesity is a disorder of energy balance. In obese individuals, there is excess body fat accumulation, which can lead to myriad health problems. The dysregulation of energy intake (appetite) and energy expenditure (activity) in obesity remains incompletely understood, but studies in humans and in model systems clearly demonstrate a strong genetic component to this condition. Within the past decade, major progress has been made in characterising the genetic component of obesity, with genome‐wide association studies revealing the most loci, including identifying the strongest association signal harboured within the FTO gene. Such studies have thus provided greater insight into the aetiology of this complex trait and are aiding in making diagnostic and therapeutic inroads into this common health concern. Key Concepts Obesity is characterised by an accumulation of excess adipose tissue that has myriad adverse health effects in virtually every organ system. The rising global prevalence of obesity, particularly in developing nations and in children, is worrisome and incompletely understood. Despite clear environmental contributions to disease risk, obesity is highly heritable. In so‐called ‘syndromic’ genetic forms of obesity, genetic changes lead to obesity along with involvement of other organ systems. In ‘non‐syndromic’ obesity, genetic changes lead to an obesity‐predominant phenotype. Animal models of these conditions have led to important insights on the hypothalamic control of appetite. Technological advances have led to the ability to perform genome‐wide association studies and identify novel genes and pathways related to obesity. The complex interaction between genetics/epigenetics and myriad factors including the microbiome, diet/environment, physical activity and circadian rhythm may hold clues as to what individualised therapeutics may improve prevention and treatment of this highly morbid condition.