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A common allele in FGF21 associated with preference for sugar consumption lowers body fat in the lower body and increases blood pressure

By Timothy M. Frayling, Robin N Beaumont, Samuel Edward Jones, Hanieh Yaghootkar, Marcus A. Tuke, Katherine S. Ruth, Francesco Casanova, Ben West, Jonathan Locke, Seth Sharp, Yingjie Ji, William Thompson, Jamie Harrison, Cecilia M Lindgren, Niels Grarup, Anna Murray, Rachel M Freathy, Michael N Weedon, Jess Tyrrell, Andrew R. Wood

Posted 06 Nov 2017
bioRxiv DOI: 10.1101/214700

Fibroblast Growth Factor 21 (FGF21) is a hormone that induces weight loss in model organisms. These findings have led to trials in humans of FGF21 analogues with some showing weight loss and lipid lowering effects. Recent genetic 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. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with body fat distribution, with less fat in the lower body, and higher blood pressure, than it is with BMI, where there is only nominal evidence of an effect. These human phenotypes of naturally occurring variation in the FGF21 gene will inform decisions about FGF21's therapeutic potential.

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