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Member Research & Reports

Member Research & Reports

UNC’s Largest-ever Genome-wide Study on Body Fat and BMI Strengthens Genetic Links to Obesity

There are many reasons why two people with the same diets and exercise regimens can gain different amounts of weight and why fat becomes stored in different parts of their bodies. Now, an international collaboration of scientists, including several from UNC’s Gillings School of Global Public Health and School of Medicine, has helped researchers hone in on genetic reasons. Their findings were published in companion papers – genome-wide association studies – in the journal Nature.

[Photo: Dr. Kari North]

Using the largest-ever set of genetic samples for the study of body fat distribution and body mass, the Genetic Investigation of Anthropometric Traits consortium of researchers – or GIANT – analyzed more than 300,000 genetic samples and found 89 new genetic locations across the genome that play roles in obesity, including body mass index and where fat is stored in the body. Previously, researchers including UNC’s Drs. Karen Mohlke and Kari North had used a smaller sample size to find 48 loci in the genome.

Finding these locations is a necessary step toward pinpointing individual genes that play major roles in traits related to obesity. If researchers find that specific genetic variants or proteins have a significant effect on body shape and size, then these genes or proteins could become targets for therapeutic interventions.

“Obesity is a worldwide public health burden with no safe and long-term treatments available,” said Dr. North, professor of epidemiology at the UNC Gillings School of Global Public Health and senior co-author of one of the Nature papers. “Our development of new therapies is limited by our lack of knowledge of the underlying pathophysiology of obesity. One novel and exciting way to identify new biology is through the study of human genetics.”

By using new computational methods, the researchers identified the 89 new genetic locations that play roles in observable traits, including waist-to-hip circumference ratio and body mass index (BMI), a measure of a person’s size based on weight and height.

Led by Dr. Mohlke, professor of genetics in the UNC School of Medicine, researchers found 33 new genetic locations associated with waist-to-hip ratio. Most people with waistlines larger than hip circumference have more visceral fat surrounding internal abdominal organs. People with this body type are more likely to have cardiovascular problems and metabolic conditions, such as Type 2 diabetes, than are people with body fat deposited more in the hip area or distributed equally throughout the body.

These waist-to-hip genetic locations are associated with genes important for the creation of adipose, or fatty, tissue. The researchers determined that 19 of the “waist-to-hip” genetic locations had a stronger effect in women; one had a stronger effect in men. Identifying these genetic locations allows scientists to search for specific variants of genes that might play roles in obesity and body fat distribution.

The two articles were published online February 11:

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