| Title: | Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study |
| Journal: | Genes |
| Published: | 19 Oct 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34681038/ |
| DOI: | https://doi.org/10.3390/genes12101644 |
| URL: | https://www.mdpi.com/2073-4425/12/10/1644/pdf?version=1634650993 |
Publication 10420
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Abstract
(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.</p>
6 Authors
- Bowen Liu
- Amy M. Mason
- Luanluan Sun
- Emanuele Di Angelantonio
- Dipender Gill
- Stephen Burgess
1 Application
| Application ID | Title |
|---|---|
| 26865 | Risk factors for `less-frequent` cardiovascular diseases |
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