Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a Mendelian randomization analysis

Dale, C. E. et al. (2017) Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a Mendelian randomization analysis. Circulation, 135(24), pp. 2373-2388. (doi: 10.1161/CIRCULATIONAHA.116.026560) (PMID:28500271) (PMCID:PMC5515354)

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Background: The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. Methods: Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Results: Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28–1.71), similar to findings for BMI (1 SD≈4.6 kg/m2; OR for CHD, 1.36; 95% CI, 1.22–1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03–1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38–2.42) and OR, 1.98 (95% CI, 1.41–2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%–77% per 1 SD). Conclusions: Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.

Item Type:Articles
Additional Information:Dr Dale is supported by a University College London Springboard Population Science Fellowship. Prof Casas is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Center. Prof Hingorani is supported by a National Institute for Health Research Senior Investigator Award. Work in his laboratory is supported by a British Heart Foundation Grant (RG/10/12/28456). The UCLEB Consortium is supported by funding from the National Institute for Health Research, British Heart Foundation (RG/10/12/28456), and Medical Research Council. Dr Holmes works in a unit that receives funds from the UK Medical Research Council.
Glasgow Author(s) Enlighten ID:Davey Smith, Professor George and Sattar, Professor Naveed
Authors: Dale, C. E., Fatemifar, G., Palmer, T. M., White, J., Prieto-Merino, D., Zabaneh, D., Engmann, J. E.L., Shah, T., Wong, A., Warren, H. R., McLachlan, S., Trompet, S., Moldovan, M., Morris, R. W., Sofat, R., Kumari, M., Hyppönen, E., Jefferis, B. J., Gaunt, T. R., Ben-Shlomo, Y., Zhou, A., Gentry-Maharaj, A., Ryan, A., Mutsert, R. d., Noordam, R., Caulfield, M. J., Jukema, J. W., Worrall, B. B., Munroe, P. B., Menon, U., Power, C., Kuh, D., Lawlor, D. A., Humphries, S. E., Mook-Kanamori, D. O., Sattar, N., Kivimaki, M., Price, J. F., Davey Smith, G., Dudbridge, F., Hingorani, A. D., Holmes, M. V., and Casas, J. P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
Journal Name:Circulation
Publisher:American Heart Association
ISSN (Online):1524-4539
Published Online:12 May 2017
Copyright Holders:Copyright © 2017 American Heart Association, Inc.
First Published:First published in Circulation 135(24): 2373-2388
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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