Observational studies have shown that elevated systolic blood pressure (SBP) is associated with future onset of type 2 diabetes, but whether this association is causal is not known. We applied the Mendelian Randomization framework to evaluate the causal hypothesis that elevated SBP increases risk to type 2 diabetes. We utilized 28 genetic variants associated with SBP and evaluated their impact on type 2 diabetes using a European-centric meta-analysis comprising 37,293 cases and 125,686 controls. We found that elevation of SBP levels by 1 mmHg due to our genetic score was associated with a 2% increase in risk of type 2 diabetes (OR=1.02, 95% CI=1.01-1.03, P=9.05x10-5). To limit confounding, we constructed a second score based on 13 variants exclusively associated with SBP and found a similar increase in type 2 diabetes risk per 1 mmHg of genetic elevation in SBP (OR=1.02, 95% CI=1.01-1.03, P=1.48x10-3). Sensitivity analyses using multiple, alternative causal inference measures and simulation studies demonstrated consistent association, suggesting robustness of our primary observation. In line with previous reports from observational studies, we found that genetically elevated SBP was associated with increased risk to type 2 diabetes. Further work will be required to elucidate the biological mechanism and translational implications.
- Received July 15, 2016.
- Accepted September 26, 2016.
- © 2016 by the American Diabetes Association.