Genetic associations with obesity overview

Introduction

Obesity results from chronic energy imbalance in a person who consistently takes in more calories from food and drink than are needed to power their body’s metabolic and physical functions. The rapidly rising population prevalence of obesity in recent decades has been attributed to an “obesogenic” environment, which offers ready access to high-calorie foods but limits opportunities for physical activity. The obesity epidemic can be considered a collective response to this environment.

Even in an obesogenic environment, however, not everyone becomes obese. Before the genomic research era, studies of family members, twins, and adoptees offered indirect scientific evidence that a sizable portion of the variation in weight among adults is due to genetic factors. For example, a key study by Stunkard AJ, et al. (The body-mass index of twins who have been reared apart. New Engl J Med 1990;332:1483-7) compared the body mass index (BMI) of twins reared either together or apart and found that inherited factors had more influence than childhood environment.

Rarely, obesity occurs in families according to a clear inheritance pattern caused by changes in a single gene. In most obese people, however, no single genetic cause can be identified. Since 2006, genome-wide association studies (GWAS) have found more than 50 loci contributing to polygenic obesity.

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