title: Systolic Blood Pressure and Risk of Type 2 Diabetes: A Mendelian Randomization Study.
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 × 10-5). 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 (odds ratio 1.02, 95% CI 1.01-1.03, P = 1.48 × 10-3). 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 for type 2 diabetes. Further work will be required to elucidate the biological mechanism and translational implications.
authors.affiliation: Department of Biology, Swarthmore College, Swarthmore, PA.
authors.forename: Rachael C
authors.initials: RC
authors.lastname: Aikens
authors.affiliation: Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.|Center for Non-Communicable Diseases, Karachi, Pakistan.|Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Danish
authors.initials: D
authors.lastname: Saleheen
authors.affiliation: Cardiology Division, Department of Medicine, and the Irving Institute for Clinical and Translational Research, Columbia University, New York, NY.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.affiliation: MedStar Heart & Vascular Institute, MedStar Washington Hospital Center, Washington, DC.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland.|Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: Emmi
authors.initials: E
authors.lastname: Tikkanen
authors.affiliation: National Institute for Health and Welfare, Department of Health, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA bvoight@upenn.edu.|Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.|Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Voight
mesh_terms: D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D015984:Causality; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D057182:Mendelian Randomization Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors; D013599:Systole; D044465:White People