Association of the FTO Obesity Risk Variant rs8050136 With Percentage of Energy Intake From Fat in Multiple Racial/Ethnic Populations

The prevalence of obesity has been increasing globally, resulting in increased rates of type 2 diabetes, cardiovascular disease, and certain cancers (1). Risk factors for obesity include a sedentary lifestyle, overconsumption of energy, and genetic susceptibility (2, 3). Recent genome-wide association studies have identified several common genetic variants associated with body mass index (BMI; weight (kg)/height (m)2), a measure of adiposity (4, 5). However, the mechanisms underlying these associations have yet to be characterized. Given that macronutrient consumption plays a key role in obesity (6), understanding the biological links between inherited genetic variation and components of energy intake may suggest strategies for reducing the increasing prevalence of obesity (7). To date, at least 32 independent loci have been found to be associated with BMI (8). Many of the genes involved, such as the brain-derived neurotrophic factor gene (BDNF), the melanocortin 4 receptor gene (MC4R), and the fat mass and obesity-associated gene (FTO), are expressed in the central nervous system (9–11), suggesting that they may act through the neurological control of various aspects of energy balance. Indeed, studies have found that obesity risk variants in intron 1 of the FTO gene are associated with greater energy consumption (12–17) or frequency of energy consumption (18) and a reduction in satiety (19–21) and intake control (12, 22, 23). In a recent study of approximately 2,100 adults of mostly European descent (77%), McCaffery et al. (18) found that FTO rs1421085 was associated with percentage of calories derived from fat. Additionally, this and another study found that obesity risk variants in the potassium channel tetramerization domain-containing 15 gene (KCTD15) and BDNF were associated with macronutrient intake (24) or increased meat and dairy intake (18). However, many of these previous studies were conducted in populations of primarily European descent. To further understand the relationship between obesity single-nucleotide polymorphisms (SNPs) and energy consumption, we investigated, as part of the Population Architecture using Genomics and Epidemiology (PAGE) Study (25), the relationship between 6 obesity risk variants and intake of macronutrients (carbohydrate, protein, ethanol, and fat and its subtypes) among type 2 diabetes-free adults from 5 racial/ethnic groups.