Obesity susceptibility loci and dietary intake in the Look AHEAD Trial

Am J Clin Nutr. 2012 Jun;95(6):1477-86. doi: 10.3945/ajcn.111.026955. Epub 2012 Apr 18.


Background: Genome-wide association studies (GWAS) have identified consistent associations with obesity. However, the mechanisms remain unclear.

Objective: The objective was to determine the association between obesity susceptibility loci and dietary intake.

Design: The association of GWAS-identified obesity risk alleles (FTO, MC4R, SH2B1, BDNF, INSIG2, TNNI3K, NISCH-STAB1, MTIF3, MAP2K5, QPCTL/GIPR, and PPARG) with dietary intake, measured through food-frequency questionnaires, was investigated in 2075 participants from the Look AHEAD (Action for Health in Diabetes) clinical trial. We adjusted for age, sex, population stratification, and study site.

Results: Obesity risk alleles at FTO rs1421085 significantly predicted more eating episodes per day (P = 0.001)-an effect that persisted after adjustment for body weight (P = 0.004). Risk variants within BDNF were significantly associated with more servings from the dairy product and the meat, eggs, nuts, and beans food groups (P ≤ 0.004). The risk allele at SH2B1 rs4788099 was significantly associated with more servings of dairy products (P = 0.001), whereas the risk allele at TNNI3K rs1514176 was significantly associated with a lower percentage of energy from protein (P = 0.002).

Conclusion: These findings suggest that obesity risk loci may affect the pattern and content of food consumption among overweight or obese individuals with type 2 diabetes. The Look AHEAD Genetic Ancillary Study was registered at clinicaltrials.gov as NCT01270763 and the Look AHEAD study as NCT00017953.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles*
  • Dairy Products
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Diet Surveys
  • Diet*
  • Dietary Proteins
  • Energy Intake / genetics*
  • Feeding Behavior / physiology*
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / genetics*
  • Risk Factors
  • Surveys and Questionnaires


  • Dietary Proteins

Associated data

  • ClinicalTrials.gov/NCT00017953
  • ClinicalTrials.gov/NCT01270763