A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure
Summary: 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 l...
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Elsevier
2018-04-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718304315 |
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doaj-8e545f5ef1c049678531993af30ecc37 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure Cell Reports |
author_facet |
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 |
author_sort |
Timothy M. Frayling |
title |
A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure |
title_short |
A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure |
title_full |
A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure |
title_fullStr |
A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure |
title_full_unstemmed |
A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure |
title_sort |
common allele in fgf21 associated with sugar intake is associated with body shape, lower total body-fat percentage, and higher blood pressure |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-04-01 |
description |
Summary: 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. : 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. Keywords: FGF21, BMI, waist-hip ratio, blood pressure, body fat, allele, genetic variant, UK Biobank |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718304315 |
work_keys_str_mv |
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doaj-8e545f5ef1c049678531993af30ecc372020-11-24T21:33:42ZengElsevierCell Reports2211-12472018-04-01232327336A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood PressureTimothy M. Frayling0Robin N. Beaumont1Samuel E. Jones2Hanieh Yaghootkar3Marcus A. Tuke4Katherine S. Ruth5Francesco Casanova6Ben West7Jonathan Locke8Seth Sharp9Yingjie Ji10William Thompson11Jamie Harrison12Amy S. Etheridge13Paul J. Gallins14Dereje Jima15Fred Wright16Yihui Zhou17Federico Innocenti18Cecilia M. Lindgren19Niels Grarup20Anna Murray21Rachel M. Freathy22Michael N. Weedon23Jessica Tyrrell24Andrew R. Wood25Genetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK; Corresponding authorGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics 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, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKThe University of North Carolina, Eshelman School of Pharmacy and Center for Pharmacogenomics and Individualized Therapy, Chapel Hill, NC, USABioinformatics Research Center, North Carolina State University, Raleigh, NC, USABioinformatics Research Center, North Carolina State University, Raleigh, NC, USABioinformatics Research Center, North Carolina State University, Raleigh, NC, USABioinformatics Research Center, North Carolina State University, Raleigh, NC, USAThe University of North Carolina, Eshelman School of Pharmacy and Center for Pharmacogenomics and Individualized Therapy, Chapel Hill, NC, USABig 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, USANovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKGenetics 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, UKGenetics of Complex Traits, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Barrack Road, Exeter EX2 5DW, UKSummary: 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. : 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. Keywords: FGF21, BMI, waist-hip ratio, blood pressure, body fat, allele, genetic variant, UK Biobankhttp://www.sciencedirect.com/science/article/pii/S2211124718304315 |