Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study
Mason, Amy M.
Di Angelantonio, Emanuele
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Liu, B., Mason, A. M., Sun, L., Di Angelantonio, E., Gill, D., & Burgess, S. (2021). Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study. [Other]. https://doi.org/10.3390/genes12101644
(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 6.5% with no diagnosed diabetes), and in participants without diabetes or pre-diabetes (HbA1c 5.7% with no diagnosed diabetes). (3) Results: Genetically-predicted T2DM liability was positively associated (p 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.
mendelian randomization, type 2 diabetes mellitus, hemoglobin A1c, average blood glucose, cardiovascular diseases
Wellcome Trust and the Royal Society (204623/Z/16/Z, RE/18/4/34215, CL-2020-16-001)
External DOI: https://doi.org/10.3390/genes12101644
This record's DOI: https://doi.org/10.17863/CAM.77144