Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference

Background: New genetic loci, most of which are expressed in the brain, have recently been reported to contribute to the development of obesity. The brain, especially the hypothalamus, is strongly involved in regulating weight and food intake. Objectives: We investigated whether the recently reported obesity loci are associated with measures of abdominal adiposity and whether these variants affect dietary energy or macronutrient intake. Design: We studied 1700 female Dutch participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Their anthropometric measurements and intake of macronutrients were available. Genotyping was performed by using KASPar chemistry. A linear regression model, with an assumption of an additive effect, was used to analyze the association between genotypes of 12 single nucleotide polymorphisms (SNPs) and adiposity measures and dietary intake. Results: Seven SNPs were associated (P < 0.05) with weight, body mass index (BMI), and waist circumference (unadjusted for BMI). They were in or near to 6 loci: FTO, MC4R, KCTD15, MTCH2, NEGR1, and BDNF. Five SNPs were associated with dietary intake (P < 0.05) and were in or near 5 loci: SH2B1 (particularly with increased fat), KCTD15 (particularly with carbohydrate intake), MTCH2, NEGR1, and BDNF. Conclusions: We confirmed some of the findings for the newly identified obesity loci that are associated with general adiposity in a healthy Dutch female population. Our results suggest that these loci are not specifically associated with abdominal adiposity but more generally with obesity. We also found that some of the SNPs were associated with macronutrient-specific food intake. Am J Clin Nutr 2009;90:951-9.