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

Laura B.L. Wittemans, Luca A. Lotta, Clare Oliver-Williams, Isobel D. Stewart, Praveen Surendran, Savita Karthikeyan, Felix R. Day, Albert Koulman, Fumiaki Imamura, Lingyao Zeng, Jeanette Erdmann, Heribert Schunkert, Kay Tee Khaw, Julian L. Griffin, Nita G. Forouhi, Robert A. Scott, Angela M. Wood, Stephen Burgess, Joanna M.M. Howson, John DaneshNicholas J. Wareham, Adam S. Butterworth, Claudia Langenberg*

*Corresponding author for this work
9 Citations (Scopus)


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.

Original languageEnglish
Article number1060
JournalNature Communications
Issue number1
Publication statusPublished - 01.12.2019

Research Areas and Centers

  • Research Area: Medical Genetics


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