A common allele in FGF21 associated with preference for sugar consumption lowers body fat in the lower body and increases blood pressure
Year: 2017
Type: preprint
Study design: Observational Study
Abstract: Summary 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.
DOI: 10.1101/214700
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, Cecilia M. Lindgren, Niels Grarup, Anna Murray, Rachel M. Freathy, Michael N. Weedon, Jessica Tyrrell, Andrew R. Wood
Institutions: University of Exeter, Royal Devon and Exeter Hospital, Exeter Hospital, Royal Devon University Healthcare NHS Foundation Trust, Broad Institute, Centre for Human Genetics, University of Oxford, University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Royal Cornwall Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Li Ka Shing Foundation, Wellcome Trust, National Institute for Health and Care Research, Diabetes Research and Wellness Foundation, Diabetes UK, National Institutes of Health, Medical Research Council, European Regional Development Fund, NIHR Oxford Biomedical Research Centre, FP7 Ideas: European Research Council
Awards: G1058688197, The causes of hyperglycaemia in the face of rising obesity, Identifying non-coding mutations in early-onset diabetes, G298712273, Using genetics to understand how the maternal intrauterine environment influences fetal growth., G5345017641, Using genetics to understand how the maternal intrauterine environment influences fetal growth., G7051768309, G7283484021, G843141311, G8737378601, G9000156922
OpenAlex ID: W2767629803