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 Danesh; Nicholas J. Wareham; Adam S. Butterworth; Claudia Langenberg

doi:10.1038/s41467-019-08936-1

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)

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.

Original language	English
Article number	1060
Journal	Nature Communications
Volume	10
Issue number	1
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-019-08936-1
Publication status	Published - 01.12.2019

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Research Area: Medical Genetics

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Wittemans, L. B. L., Lotta, L. A., Oliver-Williams, C., Stewart, I. D., Surendran, P., Karthikeyan, S., Day, F. R., Koulman, A., Imamura, F., Zeng, L., Erdmann, J., Schunkert, H., Khaw, K. T., Griffin, J. L., Forouhi, N. G., Scott, R. A., Wood, A. M., Burgess, S., Howson, J. M. M., ... Langenberg, C. (2019). Assessing the causal association of glycine with risk of cardio-metabolic diseases. Nature Communications, 10(1), Article 1060. https://doi.org/10.1038/s41467-019-08936-1

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title = "Assessing the causal association of glycine with risk of cardio-metabolic diseases",

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.",

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

year = "2019",

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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, KT, Griffin, JL, Forouhi, NG, Scott, RA, Wood, AM, Burgess, S, Howson, JMM, Danesh, J, Wareham, NJ, Butterworth, AS & Langenberg, C 2019, 'Assessing the causal association of glycine with risk of cardio-metabolic diseases', Nature Communications, vol. 10, no. 1, 1060. https://doi.org/10.1038/s41467-019-08936-1

TY - JOUR

T1 - Assessing the causal association of glycine with risk of cardio-metabolic diseases

AU - Wittemans, Laura B.L.

AU - Lotta, Luca A.

AU - Oliver-Williams, Clare

AU - Stewart, Isobel D.

AU - Surendran, Praveen

AU - Karthikeyan, Savita

AU - Day, Felix R.

AU - Koulman, Albert

AU - Imamura, Fumiaki

AU - Zeng, Lingyao

AU - Erdmann, Jeanette

AU - Schunkert, Heribert

AU - Khaw, Kay Tee

AU - Griffin, Julian L.

AU - Forouhi, Nita G.

AU - Scott, Robert A.

AU - Wood, Angela M.

AU - Burgess, Stephen

AU - Howson, Joanna M.M.

AU - Danesh, John

AU - Wareham, Nicholas J.

AU - Butterworth, Adam S.

AU - Langenberg, Claudia

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-019-08936-1

M3 - Journal articles

C2 - 30837465

AN - SCOPUS:85062584534

SN - 1751-8628

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1060

ER -

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

Abstract

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