New Genetic Variants Linked to Body Fat Distribution, Large-scale Study Finds

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by Alice Melao |

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kidney disease, obesity

A large-scale genetic screening identified 24 new genetic variants implicated in the distribution of body fat.

Conducted by researchers from the Genetic Investigation of Anthropometric Traits consortium, the study adds new information on potential genes and mechanisms involved in the regulation and distribution of body fat. It may also help identify potential risk factors of central obesity-associated disorders, such as type 2 diabetes and cardiovascular diseases.

The study, “Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution,” was published in the journal Nature Genetics.

Accumulation of fat in the abdominal region is often described as the “bad fat,” because studies have shown that larger abdominal size is associated with an increased risk of several metabolic disorders. To reduce this risk, it has been suggested that the waist-to-hip ratio (WHR) should be kept low, indicating that more fat is accumulated in the hip and gluteus areas than in the abdominal region.

Although more frequent physical activity could help manage the WHR, genetic factors also are known to play a significant role in body mass distribution.

To identify potential genes involved in the WHR body fat distribution, the researchers analyzed genetic information collected in 74 studies comprising a total of 344,369 individuals of different ancestries — including those of European, South and East Asian, African, and Hispanic/Latino descent. Results were then confirmed in a group of 132,177 people of European ancestry.

After a detailed screening analysis, the researchers identified several genetic variants linked to body fat distribution, of which 24 were new. In particular, the team identified 15 common and nine rare new and independent variants that may regulate body fat distribution.

“For the first time, we were able to examine, on a large scale, how low-frequency and rare variants influence body fat distribution,” Kari E. North, PhD, a professor at the University of North Carolina at Chapel Hill Gillings School of Global Public Health and joint lead author of the study, said in a press release. “These variants are rarer in the population, but the effects they have on individuals are much larger, possibly making them more clinically relevant.”

An analysis of the potential role of the identified genes revealed they could regulate body fat distribution by being involved in the metabolism of fatty molecules, adiponectin signaling, abnormal adipose tissue metabolism, and bone development and structure regulation.

These genes were also found to be linked to several cardiometabolic traits, and also to diet or behavioral traits potentially related to obesity.

Based on the importance of the features associated with these genes in the regulation of body fat distribution, the team decided to explore the impact of the identified genetic variants. They genetically manipulated fruit flies to carry one of 27 specific gene variants similar to those found in humans.Using this strategy, they found that variants of the PLXND1 and DNAH10 genes led to a significant increase in the amount of triglyceride — a type of active fat molecule — in the body.

“We implicate novel genes in fat distribution,” the researchers wrote, adding that the findings offer potential new therapeutic targets.

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