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

• Published in: Cell reports (Cambridge) Vol. 23; no. 2; pp. 327 - 336
• Main Authors: Frayling, Timothy M., Beaumont, Robin N., Jones, Samuel E., Yaghootkar, Hanieh, Tuke, Marcus A., Ruth, Katherine S., Casanova, Francesco, West, Ben, Locke, Jonathan, Sharp, Seth, Ji, Yingjie, Thompson, William, Harrison, Jamie, Etheridge, Amy S., Gallins, Paul J., Jima, Dereje, Wright, Fred, Zhou, Yihui, Innocenti, Federico, Lindgren, Cecilia M., Grarup, Niels, Murray, Anna, Freathy, Rachel M., Weedon, Michael N., Tyrrell, Jessica, Wood, Andrew R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.04.2018; Cell Press; Elsevier
• Subjects: Adult; Aged; Alcohol Drinking; allele; Alleles; Blood Pressure; BMI; body fat; Body Fat Distribution; Body Mass Index; Body Size; Databases, Factual; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Diet, High-Fat; FGF21; Fibroblast Growth Factors - genetics; genetic variant; Genome-Wide Association Study; Humans; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Sugars - metabolism; UK Biobank; United Kingdom; waist-hip ratio; United Kingdom; blood pressure; waist-hip ratio; allele; genetic variant; UK Biobank; FGF21; BMI; body fat
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •A human allele in FGF21 is associated with higher alcohol as well as sugar intake•Phenotypes associated with this allele likely mimic those of lower FGF21 function•The human allele in FGF21 is associated with lower total body-fat percentage•The human allele in FGF21 is associated with higher blood pressure and waist-hip ratio Drugs targeting the hormone FGF21 may have beneficial health effects. Variations in human DNA in the FGF21 gene provide an indication of what those effects may be. Here, we show that variation in the FGF21 gene is associated with higher blood pressure and altered body shape, despite lower total body-fat percentage.