{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:46:36Z","timestamp":1790304396422,"version":"4.1.0"},"reference-count":15,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust and the Royal Society","award":["204623\/Z\/16\/Z"],"award-info":[{"award-number":["204623\/Z\/16\/Z"]}]},{"name":"British Heart Foundation Centre of Research Excellence","award":["RE\/18\/4\/34215"],"award-info":[{"award-number":["RE\/18\/4\/34215"]}]},{"name":"National Institute for Health Research Clinical Lectureship","award":["CL-2020-16-001"],"award-info":[{"award-number":["CL-2020-16-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>(1) Aim: To investigate the causal effects of T2DM liability and glycated haemoglobin (HbA1c) levels on various cardiovascular disease outcomes, both in the general population and in non-diabetic individuals specifically. (2) Methods: We selected 243 variants as genetic instruments for T2DM liability and 536 variants for HbA1c. Linear Mendelian randomization analyses were performed to estimate the associations of genetically-predicted T2DM liability and HbA1c with 12 cardiovascular disease outcomes in 367,703 unrelated UK Biobank participants of European ancestries. We performed secondary analyses in participants without diabetes (HbA1c &lt; 6.5% with no diagnosed diabetes), and in participants without diabetes or pre-diabetes (HbA1c &lt; 5.7% with no diagnosed diabetes). (3) Results: Genetically-predicted T2DM liability was positively associated (p &lt; 0.004, 0.05\/12) with peripheral vascular disease, aortic valve stenosis, coronary artery disease, heart failure, ischaemic stroke, and any stroke. Genetically-predicted HbA1c was positively associated with coronary artery disease and any stroke. Mendelian randomization estimates generally shifted towards the null when excluding diabetic and pre-diabetic participants from analyses. (4) Conclusions: This genetic evidence supports causal effects of T2DM liability and HbA1c on a range of cardiovascular diseases, suggesting that improving glycaemic control could reduce cardiovascular risk in a general population, with greatest benefit in individuals with diabetes.<\/jats:p>","DOI":"10.3390\/genes12101644","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T03:01:13Z","timestamp":1634698873000},"page":"1644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Bowen","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK"},{"name":"Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-0777","authenticated-orcid":false,"given":"Amy M.","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luanluan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Di Angelantonio","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-7078","authenticated-orcid":false,"given":"Dipender","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK"},{"name":"Genetics Department, Novo Nordisk Research Centre Oxford, Old Road Campus, Oxford OX3 7FZ, UK"},{"name":"Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George\u2019s, University of London, London SW17 0RE, UK"},{"name":"Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George\u2019s University Hospitals NHS Foundation Trust, London SW17 0QT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK"},{"name":"Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge CB2 0SR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12933-018-0728-6","article-title":"Prevalence of Cardiovascular Disease in Type 2 Diabetes: A Systematic Literature Review of Scientific Evidence from across the World in 2007\u20132017","volume":"17","author":"Einarson","year":"2018","journal-title":"Cardiovasc. 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