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Assessing the causal association of glycine with risk of cardio-metabolic diseases

Title: Assessing the causal association of glycine with risk of cardio-metabolic diseases
Authors: Wittemans, LBL
Lotta, LA
Oliver-Williams, C
Stewart, ID
Surendran, P
Karthikeyan, S
Day, FR
Koulman, A
Imamura, F
Zeng, L
Erdmann, J
Schunkert, H
Khaw, K-T
Griffin, JL
Forouhi, NG
Scott, RA
Wood, AM
Burgess, S
Howson, JMM
Danesh, J
Wareham, NJ
Butterworth, AS
Langenberg, C
Item Type: Journal Article
Abstract: Circulating levels of glycine have previously been associated with lower incidence of coronary heart disease (CHD) and type 2 diabetes (T2D) but it remains uncertain if glycine plays an aetiological role. We present a meta-analysis of genome-wide association studies for glycine in 80,003 participants and investigate the causality and potential mechanisms of the association between glycine and cardio-metabolic diseases using genetic approaches. We identify 27 genetic loci, of which 22 have not previously been reported for glycine. We show that glycine is genetically associated with lower CHD risk and find that this may be partly driven by blood pressure. Evidence for a genetic association of glycine with T2D is weaker, but we find a strong inverse genetic effect of hyperinsulinaemia on glycine. Our findings strengthen evidence for a protective effect of glycine on CHD and show that the glycine-T2D association may be driven by a glycine-lowering effect of insulin resistance.
Issue Date: 5-Mar-2019
Date of Acceptance: 11-Feb-2019
URI: http://hdl.handle.net/10044/1/75271
DOI: 10.1038/s41467-019-08936-1
ISSN: 2041-1723
Publisher: Nature Research (part of Springer Nature)
Journal / Book Title: Nature Communications
Volume: 10
Issue: 1
Copyright Statement: © The Author(s) 2019. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/
Keywords: Coronary Disease
Diabetes Mellitus, Type 2
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Glycine
Humans
Hyperinsulinism
Incidence
Metabolic Networks and Pathways
Polymorphism, Single Nucleotide
Humans
Coronary Disease
Diabetes Mellitus, Type 2
Hyperinsulinism
Genetic Predisposition to Disease
Glycine
Incidence
Polymorphism, Single Nucleotide
Metabolic Networks and Pathways
Genome-Wide Association Study
Genetic Loci
Coronary Disease
Diabetes Mellitus, Type 2
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Glycine
Humans
Hyperinsulinism
Incidence
Metabolic Networks and Pathways
Polymorphism, Single Nucleotide
Publication Status: Published
Conference Place: England
Article Number: ARTN 1060
Appears in Collections:Department of Metabolism, Digestion and Reproduction