Obesity is an enormous public health concern in the United States, affecting about 33% of adults and 20% of children and adolescents. While lifestyle and environmental factors play an undeniable role in whether an individual becomes obese, researchers have also uncovered common genetic variants that influence risk for the condition. One of the best-studied variants is in the FTO gene, which has been shown to be associated with obesity in young adults. However, studies in different age groups have revealed subtle differences in the effect of the FTO variant on obesity risk.
To better characterize the effects of throughout childhood development, an international team of researchers from the Early Growth Genetics Consortium (EGGC) analyzed data from eight study populations, totaling nearly 20,000 individuals of European descent. Their results, published last week in PLoS Genetics, showed a distinct genetic association with BMI that depended on age. In older children (ages 6-13), the variant was associated with a slight increase in BMI. The opposite was true in children younger than two years.
The switch in association from lower BMI to higher BMI occurred between 4-6 years of age, corresponding with a phenomenon known as “adiposity rebound” (AR). During normal development, infants experience rapidly increasing BMI, peaking around age one, followed by decreasing BMI that bottoms out around age five before rising again. AR refers to this second rise in BMI, and the EGGC study found that the A version of was also associated with earlier AR. (See figure to the right from the EGGC paper.)
It turns out that the timing of AR can have implications later in life. Multiple studies have linked earlier AR to higher BMI in adulthood, along with increased risk for obesity-related diseases such as heart disease and type 2 diabetes. Based on their findings, the EGGC researchers suggest that the connection between the FTO gene and obesity may have less to do with a general predisposition to obesity and more to do with childhood development and timing of AR. This observation may provide greater insight into the biological mechanisms underlying obesity, though additional studies are needed to confirm and refine the EGGC results.