Dianjianyi Sun1, Tao Zhou1,2, Yoriko Heianza1, Xiang Li1, Mengyu Fan3, Vivian A Fonseca4, Lu Qi1,5,6. 1. From the Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA (D.S., T.Z., Y.H., X.L., L.Q.). 2. Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, Sichuan Province, China (T.Z.). 3. Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (M.F.). 4. Section of Endocrinology and Metabolism, Tulane University School of Medicine, New Orleans, LA (V.A.F.). 5. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (L.Q.). 6. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.).
Abstract
RATIONALE: In observational studies, type 2 diabetes mellitus (T2D) has been associated with an increased risk of hypertension, and vice versa; however, the causality between these conditions remains to be determined. OBJECTIVES: This population-based prospective cohort study sought to investigate the bidirectional causal relations of T2D with hypertension, systolic and diastolic blood pressure (BP) using Mendelian randomization (MR) analysis. METHODS AND RESULTS: After exclusion of participants free of a history of heart failure, cardiovascular disease, cardiac procedures, and non-T2D diabetes mellitus, a total of 318 664 unrelated individuals with qualified genotyping data of European descent aged 37 to 73 from UK Biobank were included. The genetically instrumented T2D and hypertension were constructed using 134 and 233 single nucleotide polymorphisms, respectively. Seven complementary MR methods were applied, including inverse-variance weighted method, 2 median-based methods (simple and weighted), MR-Egger, MR-robust adjusted profile scores, MR-Pleiotropy Residual Sum and Outlier, and multivariate MR. The genetically instrumented T2D was associated with risk of hypertension (odds ratio, 1.07 [95% CI, 1.04-1.10], P=3.4×10-7), whereas the genetically determined hypertension showed no relationship with T2D (odds ratio, 0.96 [0.88-1.04], P=0.34). Our MR estimates from T2D to BP showed that the genetically instrumented T2D was associated with a 0.67 mm Hg higher systolic BP (95% CI, 0.41-0.93, P=5.75×10-7) but not with a higher diastolic BP. There was no clear evidence showing a causal effect of elevated systolic BP or diastolic BP on T2D risk. Positive pleiotropic bias was indicated in the hypertension→T2D relation (odds ratio, of MR-Egger intercept 1.010 [1.004-1.016], P=0.001) but not from T2D to hypertension (1.001 [0.998-1.004], P=0.556). CONCLUSIONS: T2D may causally affect hypertension, whereas the relationship from hypertension to T2D is unlikely to be causal. These findings suggest the importance of keeping an optimal glycemic profile in general populations, and BP screening and monitoring, especially systolic BP, in patients with T2D.
RATIONALE: In observational studies, type 2 diabetes mellitus (T2D) has been associated with an increased risk of hypertension, and vice versa; however, the causality between these conditions remains to be determined. OBJECTIVES: This population-based prospective cohort study sought to investigate the bidirectional causal relations of T2D with hypertension, systolic and diastolic blood pressure (BP) using Mendelian randomization (MR) analysis. METHODS AND RESULTS: After exclusion of participants free of a history of heart failure, cardiovascular disease, cardiac procedures, and non-T2D diabetes mellitus, a total of 318 664 unrelated individuals with qualified genotyping data of European descent aged 37 to 73 from UK Biobank were included. The genetically instrumented T2D and hypertension were constructed using 134 and 233 single nucleotide polymorphisms, respectively. Seven complementary MR methods were applied, including inverse-variance weighted method, 2 median-based methods (simple and weighted), MR-Egger, MR-robust adjusted profile scores, MR-Pleiotropy Residual Sum and Outlier, and multivariate MR. The genetically instrumented T2D was associated with risk of hypertension (odds ratio, 1.07 [95% CI, 1.04-1.10], P=3.4×10-7), whereas the genetically determined hypertension showed no relationship with T2D (odds ratio, 0.96 [0.88-1.04], P=0.34). Our MR estimates from T2D to BP showed that the genetically instrumented T2D was associated with a 0.67 mm Hg higher systolic BP (95% CI, 0.41-0.93, P=5.75×10-7) but not with a higher diastolic BP. There was no clear evidence showing a causal effect of elevated systolic BP or diastolic BP on T2D risk. Positive pleiotropic bias was indicated in the hypertension→T2D relation (odds ratio, of MR-Egger intercept 1.010 [1.004-1.016], P=0.001) but not from T2D to hypertension (1.001 [0.998-1.004], P=0.556). CONCLUSIONS:T2D may causally affect hypertension, whereas the relationship from hypertension to T2D is unlikely to be causal. These findings suggest the importance of keeping an optimal glycemic profile in general populations, and BP screening and monitoring, especially systolic BP, in patients with T2D.
Authors: Ian H de Boer; Sripal Bangalore; Athanase Benetos; Andrew M Davis; Erin D Michos; Paul Muntner; Peter Rossing; Sophia Zoungas; George Bakris Journal: Diabetes Care Date: 2017-09 Impact factor: 19.112
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Authors: Andrew P Morris; Benjamin F Voight; Tanya M Teslovich; Teresa Ferreira; Ayellet V Segrè; Valgerdur Steinthorsdottir; Rona J Strawbridge; Hassan Khan; Harald Grallert; Anubha Mahajan; Inga Prokopenko; Hyun Min Kang; Christian Dina; Tonu Esko; Ross M Fraser; Stavroula Kanoni; Ashish Kumar; Vasiliki Lagou; Claudia Langenberg; Jian'an Luan; Cecilia M Lindgren; Martina Müller-Nurasyid; Sonali Pechlivanis; N William Rayner; Laura J Scott; Steven Wiltshire; Loic Yengo; Leena Kinnunen; Elizabeth J Rossin; Soumya Raychaudhuri; Andrew D Johnson; Antigone S Dimas; Ruth J F Loos; Sailaja Vedantam; Han Chen; Jose C Florez; Caroline Fox; Ching-Ti Liu; Denis Rybin; David J Couper; Wen Hong L Kao; Man Li; Marilyn C Cornelis; Peter Kraft; Qi Sun; Rob M van Dam; Heather M Stringham; Peter S Chines; Krista Fischer; Pierre Fontanillas; Oddgeir L Holmen; Sarah E Hunt; Anne U Jackson; Augustine Kong; Robert Lawrence; Julia Meyer; John R B Perry; Carl G P Platou; Simon Potter; Emil Rehnberg; Neil Robertson; Suthesh Sivapalaratnam; Alena Stančáková; Kathleen Stirrups; Gudmar Thorleifsson; Emmi Tikkanen; Andrew R Wood; Peter Almgren; Mustafa Atalay; Rafn Benediktsson; Lori L Bonnycastle; Noël Burtt; Jason Carey; Guillaume Charpentier; Andrew T Crenshaw; Alex S F Doney; Mozhgan Dorkhan; Sarah Edkins; Valur Emilsson; Elodie Eury; Tom Forsen; Karl Gertow; Bruna Gigante; George B Grant; Christopher J Groves; Candace Guiducci; Christian Herder; Astradur B Hreidarsson; Jennie Hui; Alan James; Anna Jonsson; Wolfgang Rathmann; Norman Klopp; Jasmina Kravic; Kaarel Krjutškov; Cordelia Langford; Karin Leander; Eero Lindholm; Stéphane Lobbens; Satu Männistö; Ghazala Mirza; Thomas W Mühleisen; Bill Musk; Melissa Parkin; Loukianos Rallidis; Jouko Saramies; Bengt Sennblad; Sonia Shah; Gunnar Sigurðsson; Angela Silveira; Gerald Steinbach; Barbara Thorand; Joseph Trakalo; Fabrizio Veglia; Roman Wennauer; Wendy Winckler; Delilah Zabaneh; Harry Campbell; Cornelia van Duijn; Andre G Uitterlinden; Albert Hofman; Eric Sijbrands; Goncalo R Abecasis; Katharine R Owen; Eleftheria Zeggini; Mieke D Trip; Nita G Forouhi; Ann-Christine Syvänen; Johan G Eriksson; Leena Peltonen; Markus M Nöthen; Beverley Balkau; Colin N A Palmer; Valeriya Lyssenko; Tiinamaija Tuomi; Bo Isomaa; David J Hunter; Lu Qi; Alan R Shuldiner; Michael Roden; Ines Barroso; Tom Wilsgaard; John Beilby; Kees Hovingh; Jackie F Price; James F Wilson; Rainer Rauramaa; Timo A Lakka; Lars Lind; George Dedoussis; Inger Njølstad; Nancy L Pedersen; Kay-Tee Khaw; Nicholas J Wareham; Sirkka M Keinanen-Kiukaanniemi; Timo E Saaristo; Eeva Korpi-Hyövälti; Juha Saltevo; Markku Laakso; Johanna Kuusisto; Andres Metspalu; Francis S Collins; Karen L Mohlke; Richard N Bergman; Jaakko Tuomilehto; Bernhard O Boehm; Christian Gieger; Kristian Hveem; Stephane Cauchi; Philippe Froguel; Damiano Baldassarre; Elena Tremoli; Steve E Humphries; Danish Saleheen; John Danesh; Erik Ingelsson; Samuli Ripatti; Veikko Salomaa; Raimund Erbel; Karl-Heinz Jöckel; Susanne Moebus; Annette Peters; Thomas Illig; Ulf de Faire; Anders Hamsten; Andrew D Morris; Peter J Donnelly; Timothy M Frayling; Andrew T Hattersley; Eric Boerwinkle; Olle Melander; Sekar Kathiresan; Peter M Nilsson; Panos Deloukas; Unnur Thorsteinsdottir; Leif C Groop; Kari Stefansson; Frank Hu; James S Pankow; Josée Dupuis; James B Meigs; David Altshuler; Michael Boehnke; Mark I McCarthy Journal: Nat Genet Date: 2012-08-12 Impact factor: 38.330
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