It’s no secret that obesity rates are rising — quickly. Between 2000 and 2005 the prevalence of obesity rose by 24%. Extreme cases increased by more than 50%. If current trends continue, more than half of all Americans will be clinically obese by the year 2030.
Rapid changes in the prevalence of a disorder suggest that environmental rather than genetic factors are to blame. But scientists know from twin and adoption studies that body mass index (BMI) is highly heritable.
So which is it: nature or nurture?
As with many aspects of human health, it’s both. Some people have the bad luck to have inherited genetic variations that together with the modern environment — sedentary jobs and hobbies, easy access to calorie-dense foods — create the perfect storm for gaining weight.
Changing the environmental factors that lead to obesity in some people seems simple enough — more exercise, less food. But public health campaigns touting these commonsense fixes have had little effect against the obesity epidemic. By understanding the genetic aspects of obesity, and how they interact with the environment, scientists may be able to develop more effective treatments and prevention strategies.
In the July issue of Nature Reviews Genetics Andrew J. Walley of Imperial College London and colleagues review the current state of obesity genetics research. While much progress has been made, the authors make it clear that there is still a long way to go, as the genes identified thus far explain only a tiny fraction of the total genetic component.
One key to future advancements in obesity genetics research, say Walley et al., lies in improvements to current genomewide association study (GWAS) methods.
First, the authors recommend that researchers focus on recruiting extremely obese people for their studies to increase the likelihood of finding genes with large effects. They also suggest that scientists should stop using BMI as their primary measurement of obesity. While simple and cheap, this method does not take fat distribution or the ratio of fat to muscle into account. There are more sophisticated methods, such as CT scans, MRI scans and ultrasound imaging, as well as machines that use air displacement to measure body volume and weight and can calculate fat and fat-free body mass. Technological advances that will reduce the costs associated with genotyping, and ultimately genetic sequencing, are also needed so that larger numbers of subjects can be studied.
Beyond these improvements to current GWAS methods, Walley et al. say studies of more than just common variations are needed. They suggest that investigations of rare SNPs, copy number variations (duplications, insertions and deletions of DNA) and inherited changes that don’t affect the actual DNA sequence will be needed to fully understand the genetics of obesity.
There are several competing theories about the overall biological basis of obesity. Some suggest that obesity is a disorder of energy balance in the body, while others think regulation of the growth of fat cells is the key. Still others think obesity may be due to defects in the neurological control of appetite and food intake. Continued advancements in understanding the genetics of obesity will help scientists tease these theories apart, and hopefully lead to a healthier future.
