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

Accepted version
Peer-reviewed

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Authors

Wittemans, Laura BL 
Lotta, Luca A 
Oliver-Williams, Clare 
Stewart, Isobel D 
Surendran, Praveen 

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.

Description

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

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MC_UU_12015/5)
British Heart Foundation (None)
British Heart Foundation (None)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
MRC (MC_PC_13046)
MRC (MC_PC_13048)
Medical Research Council (MR/P011705/1)
Medical Research Council (MR/P01836X/1)
Medical Research Council (G0401527)
Medical Research Council (G1000143)
Medical Research Council (MR/N003284/1)
Medical Research Council (MR/S003746/1)
Medical Research Council (MR/L003120/1)
European Research Council (268834)
Medical Research Council (G0800270)
Medical Research Council (MC_UU_12015/2)
Medical Research Council (MC_UU_00002/7)
British Heart Foundation (RG/18/13/33946)
Medical Research Council (MC_PC_13030)
Biotechnology and Biological Sciences Research Council (BB/M027252/2)
Biotechnology and Biological Sciences Research Council (BB/P028195/1)
Biotechnology and Biological Sciences Research Council (BB/M027252/1)
Medical Research Council (G0700463)
Wellcome Trust (204623/Z/16/Z)
Medical Research Council (G0700463/1)
Medical Research Council (G0800270/1)
Medical Research Council (G0401527/1)
Cancer Research Uk (None)
Medical Research Council (MC_PC_13048)
Medical Research Council (MC_PC_13046)
N. G. F. and F.I. acknowledge funding from Medical Research Council Epidemiology Unit MC_UU_12015/5. N.G.F. and N. J. W. acknowledge funding from the NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). S. B. is supported by Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z). J. D. is funded by the National Institute for Health Research [Senior Investigator Award]. N. J. W. and C. L. acknowledge funding from the Medical Research Council Epidemiology Unit (MC_UU_12015/1).