Citation: Diabetes. 66(2):543-550, 2017 Feb.Journal: Diabetes.Published: 2017ISSN: 0012-1797.Full author list: Aikens RC; Zhao W; Saleheen D; Reilly MP; Epstein SE; Tikkanen E; Salomaa V; Voight BF.UI/PMID: 27702834.Subject(s): *Blood Pressure/ge [Genetics] | Case-Control Studies | Causality | Diabetes Mellitus, Type 2/ep [Epidemiology] | *Diabetes Mellitus, Type 2/ge [Genetics] | European Continental Ancestry Group | Genetic Variation | Humans | Mendelian Randomization Analysis | Odds Ratio | Polymorphism, Single Nucleotide | Regression Analysis | Risk Factors | SystoleInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.2337/db16-0868 (Click here)Abbreviated citation: Diabetes. 66(2):543-550, 2017 Feb.Local Holdings: Available online from MWHC library: 1995 - present (after 3 months), Available in print through MWHC library: 1999 - 2006.Abstract: 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 for type 2 diabetes. We used 28 genetic variants associated with SBP and evaluated their impact on type 2 diabetes using a European-centric meta-analysis comprising 37,293 case and 125,686 control subjects. 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 (odds ratio 1.02, 95% CI 1.01-1.03, P = 9.05 x 10<sup>-5</sup>). 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 (odds ratio 1.02, 95% CI 1.01-1.03, P = 1.48 x 10<sup>-3</sup>). 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 for type 2 diabetes. Further work will be required to elucidate the biological mechanism and translational implications.Abstract: Copyright � 2017 by the American Diabetes Association.