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Abstract
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.
26 Authors
Timothy M. Frayling
Robin N. Beaumont
Samuel E. Jones
Hanieh Yaghootkar
Marcus A. Tuke
Katherine S. Ruth
Francesco Casanova
Ben West
Jonathan Locke
Seth Sharp
Yingjie Ji
William Thompson
Jamie Harrison
Amy S. Etheridge
Paul J. Gallins
Dereje Jima
Fred Wright
Yihui Zhou
Federico Innocenti
Cecilia M. Lindgren
Niels Grarup
Anna Murray
Rachel M. Freathy
Michael N. Weedon
Jessica Tyrrell
Andrew R. Wood
Enabling scientific discoveries that improve human health