The largest studies to date of genetic links to obesity and body-fat distribution have discovered more than 140 locations in the genome that play a role in obesity traits. These studies, published in Nature on 11 February 2015, have shed new light on the biological pathways important in controlling metabolism and appetite.
The participants in the GIANT (Genetic Investigation of Anthropomorphic Traits) consortium, which carried out the studies, include Cecilia Lindgren, Mark McCarthy and members of their groups at the Wellcome Trust Centre for Human Genetics. By integrating genome-wide association data from a number of different initiatives worldwide, the consortium has been able build up a sample of more than 300,000 individuals with and without obesity-related traits.
One study looked at the ratio of waist and hip measurements as an indication of where fat is stored in the body. People with large amounts of belly fat are more likely to have metabolic conditions such as Type 2 diabetes, and more likely to have cardiovascular problems, than those with more fat in the hip area or distributed more evenly around the body.
The researchers found that the distribution of body fat was linked to genetic regions previously associated with the creation of fatty tissue. The effect at 19 of these locations was stronger in women than in men, while only one location had a stronger effect in men. ‘By finding genetic variants that play an important role in influencing body fat distribution and the ways in which fat distribution differs between men and women, we hope to zoom in on the crucial underlying biological processes,’ said Cecilia Lindgren, currently Scholar in Residence at the Broad Institute at MIT.
The second study tripled the number of known associations with body mass index (BMI), a measure of weight relative to height. Using new computational methods, the researchers were able to identify that a number of these locations were involved in brain signalling that controls appetite and energy use.
The large number of known locations that increase the genetic risk of obesity and related conditions collectively exert a relatively small effect, meaning that there is still a great deal more to learn. However, the novel pathways revealed by the research may begin to explain how appetite and metabolism are controlled, a first step towards targeted therapies.