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

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

Author information

1
Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK. Electronic address: t.m.frayling@exeter.ac.uk.
2
Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK.
3
Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK; Diabetes and Vascular Research Centre, University of Exeter Medical School, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK.
4
The University of North Carolina, Eshelman School of Pharmacy and Center for Pharmacogenomics and Individualized Therapy, Chapel Hill, NC, USA.
5
Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA.
6
Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
7
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
8
Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK; European Centre for Environment and Human Health, University of Exeter Medical School, The Knowledge Spa, Royal Cornwall Hospital, Truro TR1 3HD, UK.

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.

KEYWORDS:

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

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