Year: 2019
Type: review
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.
Source: Nature Communications
Authors: 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
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Centre International de Recherche sur le Cancer, NHS Blood and Transplant, Wellcome Trust, European Federation of Pharmaceutical Industries and Associations, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, Department of Health and Social Care, University of Cambridge, European Commission, Cambridge University Hospitals, Innovative Medicines Initiative, NIHR BioResource, Medical Research Council, Biotechnology and Biological Sciences Research Council, NIHR Cambridge Biomedical Research Centre, FP7 Ideas: European Research Council
Awards: Genetics and causality: towards more accessible and more reliable Mendelian randomization investigations, G1073258374, Aetiology of type 2 diabetes and related metabolic disorders, G1093531541, Nutritional epidemiology, High Throughput Science - Investigating pathways to metabolic disease using "omic" approaches, G1305685332, G1553864662, G160417252, Macronutrients and Metabolic Health - Understanding how metabolic disease arises at the population level using metabolomics and lipidomics., G1671907826, G1732308444, NIHR Senior Investigator Award, G1953244154, High Throughput Science - Investigating the genetic determinants of healthy ageing: the MRC EPIC-Norfolk study, The validation of biomarkers of metabolic efficacy in infant nutrition, G2250148255, Large-scale integrative genomic studies of high-dimensional traits in cardiovascular diseases (renewal), G2473961061, The Cambridge Initiative: Proposal to enhance linked research in human fat metabolism and pathophysiology between MRC HNR, MRC MDU and MRC Epi, G2531204615, G2804450655, G2892497062, G3077395769, G3084320185, G3207356259, MRC Cambridge Lipidomics Biomarker Research Initiative (CLBRI), G3715519340, G3812975344, G385907487, G393177772, G3986547339, G4194769985, Systematic characterisation of genetically influenced 'omics' phenotypes and disease modules within biological networks, G43956866, G4733990475, The EPIC-Norfolk prospective population study: biological and behavioural determinants of health and disease in an ageing population, Proposal to enhance linked research in human fat metabolism & pathophysiology between MRC HNR, MRC MDU and MRC EU, G567453067, G5702163051, G5787426001, G587296758, G5897142711, NIHR Senior Investigator Award, HDHL-Biomarkers: Biomarkers for Infant Fat Mass Development and Nutrition (BioFN), G6382720711, EPIC-CVD: Individualised CVD risk assessment: tailoring targeted and cost-effective approaches to Europe's diverse populations, G6548202893, G6870695443, G7461028278, Interplay of genetic, nutrient and lifestyle factors on incidence of coronary disease: EPIC-Heart, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application (renewal). (Joint funding with MRC), G762219591, G7939076303, The validation of biomarkers of metabolic efficacy in infant nutrition, European Medical Information Framework, G8346449347, RENEWAL: Systematic approaches to the evaluation of emerging coronary risk markers. Large-scale epidemiological analyses of existing data and stored biological samples, G8585681489, NIHR Senior Investigator Award, Child Growth and development, G8909929916, G8975348055, G9000040826, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application
OpenAlex ID: W2920425752