Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study

Am J Epidemiol. 2013 Sep 1;178(5):780-90. doi: 10.1093/aje/kwt028. Epub 2013 Jul 2.

Abstract

Common obesity risk variants have been associated with macronutrient intake; however, these associations' generalizability across populations has not been demonstrated. We investigated the associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies: the Multiethnic Cohort Study (1993-2006) (n = 19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n = 11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n = 6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n = 36,973) was positively associated with percentage of calories derived from fat (βmeta = 0.2244 (standard error, 0.0548); P = 4 × 10(-5)) and inversely associated with percentage of calories derived from carbohydrate (βmeta = -0.2796 (standard error, 0.0709); P = 8 × 10(-5)). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m)(2)) obtained at 10 years of follow-up (mediation of effect = 0.0823 kg/m(2), 95% confidence interval: 0.0559, 0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.

Keywords: energy intake; fat mass and obesity-associated (FTO) gene; obesity; percent calories from fat; race/ethnicity.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Continental Population Groups / genetics*
  • Diet
  • Dietary Fats / administration & dosage*
  • Energy Intake*
  • Ethnic Groups / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Obesity / ethnology
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Proteins / genetics*
  • Risk Factors

Substances

  • Dietary Fats
  • Proteins
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human

Grant support