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Genetically proxied growth-differentiation factor 15 levels and body mass index.

Karhunen, V; Larsson, SC; Gill, D (2021) Genetically proxied growth-differentiation factor 15 levels and body mass index. Br J Clin Pharmacol, 87 (10). pp. 4036-4039. ISSN 1365-2125 https://doi.org/10.1111/bcp.14808
SGUL Authors: Gill, Dipender Preet Singh

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Abstract

Growth-differentiation factor 15 (GDF15) is an inflammatory cytokine involved in energy homeostasis that is being pursued as a drug target for obesity. Its circulating levels are acutely increased by the type 2 diabetes medication metformin, resulting in reduced appetite and weight loss. We identified a genetic variant at the GDF15 gene to proxy a small, lifelong increase in circulating GDF15 levels, and leveraged it in colocalization and Mendelian randomization analyses to investigate the effects of chronically elevated GDF15 levels on body mass index (BMI) and type 2 diabetes liability. The results provide human genetic evidence supporting that chronically elevated GDF15 levels increase BMI. There was no genetic evidence to support bi-directional effects, or that chronically elevated GDF15 levels directly affect liability to type 2 diabetes. Our results contrast the BMI-lowering effects of an acute increase in GDF15 levels observed after metformin use. These findings have direct implications for informing pharmacological strategies aimed at targeting GDF15 levels for weight loss.

Item Type: Article
Additional Information: © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Mendelian randomization, body mass index, colocalization, growth-differentiation factor 15, type 2 diabetes, Mendelian randomization, body mass index, colocalization, growth-differentiation factor 15, type 2 diabetes, Pharmacology & Pharmacy, 1115 Pharmacology and Pharmaceutical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Br J Clin Pharmacol
ISSN: 1365-2125
Language: eng
Dates:
DateEvent
23 September 2021Published
19 March 2021Published Online
25 February 2021Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
RE/18/4/34215British Heart FoundationUNSPECIFIED
CL-2020-16-001Research Trainees Coordinating CentreUNSPECIFIED
2018-00123Swedish Research Council for Health, Working Life and WelfareUNSPECIFIED
20190247Swedish Heart-Lung FoundationUNSPECIFIED
2019-00977Swedish Research CouncilUNSPECIFIED
UNSPECIFIEDSt. George's, University of LondonUNSPECIFIED
UNSPECIFIEDNational Institute for Health ResearchUNSPECIFIED
UNSPECIFIEDImperial College LondonUNSPECIFIED
PubMed ID: 33686698
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/113045
Publisher's version: https://doi.org/10.1111/bcp.14808

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