Macronutrient intake as a mediator with FTO to increase body mass index

J Am Coll Nutr. 2014;33(4):256-66. doi: 10.1080/07315724.2013.879458. Epub 2014 Aug 21.

Abstract

Background: The fat mass and obesity-associated (FTO) single nucleotide polymorphisms (SNPs; rs1421085, rs17817449, rs9939609, rs8050136) and macronutrient intake (carbohydrate, protein, fat, total calories) are associated with body mass index (BMI). However, the mechanism for this relationship has not been fully elucidated.

Objective: This study examined whether macronutrient intake mediates the association between FTO SNPs and BMI.

Design: Baseline cross-sectional data from the Atherosclerosis Risk in Communities (ARIC) study of whites (n = 10,176) and African Americans (n = 3641) aged 45 to 64 years were analyzed.

Results: In linear regression models with BMI as the dependent variable, FTO SNPs were significantly associated with higher BMI after adjusting for covariates. The addition of energy-adjusted macronutrients attenuated the FTO effect estimates, indicating partial mediation. In whites, β ranged from 0.40 (95% confidence interval [CI], 0.20, 0.60) for rs17817449 heterozygous carriers to 0.93 (95% CI, 0.64, 122) for rs8050136 homozygous carriers; for African Americans rs17817449 homozygous carriers β was 0.65 (95% CI, 0.03, 1.27). In models with macronutrient intake as the dependent variable, all FTO SNPs were associated with higher protein intake for homozygous carriers after adjusting for BMI and other covariates. Among whites, β ranged from 1.44 (95% CI, 0.51, 2.37) for rs8050136 to 1.73 (95% CI, 0.85, 2.61) for rs17817449; among African American rs8050136 homozygous carriers β was 2.46 (95% CI, 0.77, 4.14). In mediation analysis, in whites only, FTO high-risk alleles were associated with higher BMI partly through their small effects on carbohydrate and protein intake.

Conclusions: These findings suggest that in adults, the relationship between FTO variants and BMI is not primarily through mediation of food intake.

Keywords: FTO; body mass index; macronutrient; mediation; race.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • African Americans / genetics
  • Aged
  • Alleles
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Body Mass Index*
  • Cross-Sectional Studies
  • Dietary Carbohydrates / administration & dosage
  • Dietary Fats / administration & dosage
  • Dietary Proteins / administration & dosage
  • Energy Intake*
  • European Continental Ancestry Group / genetics
  • Female
  • Homozygote
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Proteins / genetics*
  • Proteins / metabolism
  • Surveys and Questionnaires

Substances

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