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Genetically Predicted Type 2 Diabetes Mellitus Liability, Glycated Hemoglobin and Cardiovascular Diseases: A Wide-Angled Mendelian Randomization Study
- Source :
- Genes, Vol 12, Iss 1644, p 1644 (2021), Genes
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
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.
- Subjects :
- Male
medicine.medical_specialty
endocrine system diseases
type 2 diabetes mellitus
Population
Coronary Artery Disease
QH426-470
Coronary artery disease
chemistry.chemical_compound
Internal medicine
Diabetes mellitus
Mendelian randomization
Genetics
medicine
Humans
Genetic Predisposition to Disease
education
Stroke
hemoglobin A1c
Genetics (clinical)
Genetic Association Studies
average blood glucose
Ischemic Stroke
Genetics & Heredity
Glycated Hemoglobin
Heart Failure
Peripheral Vascular Diseases
0604 Genetics
education.field_of_study
Science & Technology
business.industry
Vascular disease
Communication
Type 2 Diabetes Mellitus
nutritional and metabolic diseases
Genetic Variation
Aortic Valve Stenosis
Mendelian Randomization Analysis
Middle Aged
medicine.disease
cardiovascular diseases
chemistry
Diabetes Mellitus, Type 2
mendelian randomization
Female
Glycated hemoglobin
business
Life Sciences & Biomedicine
Subjects
Details
- ISSN :
- 20734425
- Database :
- OpenAIRE
- Journal :
- Genes, Vol 12, Iss 1644, p 1644 (2021), Genes
- Accession number :
- edsair.doi.dedup.....e68e990df55c60cb53d77b2ba1765e47