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

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 participant...

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Main Authors: Wittemans, L, Lotta, L, Oliver-Williams, C, Stewart, I, Surendran, P, Karthikeyan, S, Day, F, Koulman, A, Imamura, F, Zeng, L, Erdmann, J, Schunkert, H, Khaw, K, Griffin, J, Forouhi, N, Scott, R, Wood, A, Burgess, S, Howson, J, Danesh, J, Wareham, N, Butterworth, A, Langenberg, C
Format: Journal article
Language:English
Published: Nature Research 2019
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author Wittemans, L
Lotta, L
Oliver-Williams, C
Stewart, I
Surendran, P
Karthikeyan, S
Day, F
Koulman, A
Imamura, F
Zeng, L
Erdmann, J
Schunkert, H
Khaw, K
Griffin, J
Forouhi, N
Scott, R
Wood, A
Burgess, S
Howson, J
Danesh, J
Wareham, N
Butterworth, A
Langenberg, C
author_facet Wittemans, L
Lotta, L
Oliver-Williams, C
Stewart, I
Surendran, P
Karthikeyan, S
Day, F
Koulman, A
Imamura, F
Zeng, L
Erdmann, J
Schunkert, H
Khaw, K
Griffin, J
Forouhi, N
Scott, R
Wood, A
Burgess, S
Howson, J
Danesh, J
Wareham, N
Butterworth, A
Langenberg, C
author_sort Wittemans, L
collection OXFORD
description 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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spelling oxford-uuid:10ce9c01-a3d4-45f0-8ca9-d1c497a96f1b2022-03-26T09:58:32ZAssessing the causal association of glycine with risk of cardio-metabolic diseasesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:10ce9c01-a3d4-45f0-8ca9-d1c497a96f1bEnglishSymplectic Elements at OxfordNature Research2019Wittemans, LLotta, LOliver-Williams, CStewart, ISurendran, PKarthikeyan, SDay, FKoulman, AImamura, FZeng, LErdmann, JSchunkert, HKhaw, KGriffin, JForouhi, NScott, RWood, ABurgess, SHowson, JDanesh, JWareham, NButterworth, ALangenberg, CCirculating 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.
spellingShingle Wittemans, L
Lotta, L
Oliver-Williams, C
Stewart, I
Surendran, P
Karthikeyan, S
Day, F
Koulman, A
Imamura, F
Zeng, L
Erdmann, J
Schunkert, H
Khaw, K
Griffin, J
Forouhi, N
Scott, R
Wood, A
Burgess, S
Howson, J
Danesh, J
Wareham, N
Butterworth, A
Langenberg, C
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
title_full Assessing the causal association of glycine with risk of cardio-metabolic diseases
title_fullStr Assessing the causal association of glycine with risk of cardio-metabolic diseases
title_full_unstemmed Assessing the causal association of glycine with risk of cardio-metabolic diseases
title_short Assessing the causal association of glycine with risk of cardio-metabolic diseases
title_sort assessing the causal association of glycine with risk of cardio metabolic diseases
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