March 30, 2015European Heart Journal
Mendelian randomization analysis supports the causal role of dysglycaemia and diabetes in the risk of coronary artery disease
Why the study?
Do genetic variants associated with dysglycaemia and diabetes increase the risk of coronary artery disease?
Population
Genetic data from Meta-Analyses of Glucose and Insulin-Related Traits Consortium, Diabetes Genetics…
Authors
Discussion
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Member takes
Implication
Supports causal diabetes-CAD link via MR; leaves open whether glucose lowering reduces events.
Key Points
- To assess whether genetic evidence supports a causal relationship between dysglycaemia, type 2 diabetes, and the risk of coronary artery disease.
- Extracted effect estimates for single nucleotide polymorphisms associated with fasting glucose, glycated haemoglobin (HbA1c), and diabetes from the MAGIC and DIAGRAM consortia.
- Evaluated the causal effects of these genetic variants on coronary artery disease risk using summary-level data from the CARDIOGRAMplusC4D consortium.
- Genetically predicted type 2 diabetes across 59 genetic variants was significantly associated with increased risk of coronary artery disease (OR: 1.63, 95% CI: 1.23–2.07; P = 0.002).
- Nine genetic variants for HbA1c were associated with coronary artery disease (OR: 1.53 per 1% increase, 95% CI: 1.14–2.05; P = 0.023), whereas 30 variants for fasting glucose were not significantly associated (OR: 1.18 per mmol/L, 95% CI: 0.97–1.42; P = 0.102).
- Stratification of genetic loci by mechanisms of β-cell dysfunction versus insulin resistance showed no significant differences in coronary artery disease risk.
Structured PICO
Do genetic variants associated with dysglycaemia and diabetes increase the risk of coronary artery disease?
P
Population
Genetic data from Meta-Analyses of Glucose and Insulin-Related Traits Consortium, Diabetes Genetics Replication and Meta-Analysis consortia, and CARDIOGRAMplusC4D
I
Intervention
Genetic variants (SNPs) associated with fasting glucose (FG), glycated haemoglobin (HbA1c), and diabetes
O
Outcome
Risk of coronary artery disease (CAD)hard clinical
Mendelian randomization supports a causal role for diabetes and elevated HbA1c in increasing the risk of coronary artery disease, suggesting long-term glucose lowering may reduce CAD events.
Cite This Study
Ross et al. (2015) studied this question.