A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure

Cell Rep. 2018 Apr 10;23(2):327-336. doi: 10.1016/j.celrep.2018.03.070.


Fibroblast growth factor 21 (FGF21) is a hormone that has insulin-sensitizing properties. Some trials of FGF21 analogs show weight loss and lipid-lowering effects. Recent studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed, but there was little evidence of an effect on metabolic traits. We studied a common FGF21 allele (A:rs838133) in 451,099 people from the UK Biobank study, aiming to use the human allele to inform potential adverse and beneficial effects of targeting FGF21. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with higher blood pressure and waist-hip ratio, despite an association with lower total body-fat percentage, than it is with BMI or type 2 diabetes. These human phenotypes of variation in the FGF21 gene will inform research into FGF21's mechanisms and therapeutic potential.

Keywords: BMI; FGF21; UK Biobank; allele; blood pressure; body fat; genetic variant; waist-hip ratio.

MeSH terms

  • Adult
  • Aged
  • Alcohol Drinking
  • Alleles
  • Blood Pressure*
  • Body Fat Distribution*
  • Body Mass Index
  • Body Size
  • Databases, Factual
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Diet, High-Fat
  • Fibroblast Growth Factors / genetics*
  • Genome-Wide Association Study
  • Humans
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Sugars / metabolism*
  • United Kingdom


  • Sugars
  • fibroblast growth factor 21
  • Fibroblast Growth Factors