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Causal Associations of Adiposity and Body Fat Distribution with Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis

Dale, CE and Fatemifar, G and Palmer, TM and White, J and Prieto-Merino, D and Zabaneh, D and Engmann, JEL and Shah, T and Wong, A and Warren, HR and McLachlan, S and Trompet, S and Moldovan, M and Morris, RW and Sofat, R and Kumari, M and Hyppönen, E and Jefferis, BJ and Gaunt, TR and Ben-Shlomo, Y and Zhou, A and Gentry-Maharaj, A and Ryan, A and Mutsert, RD and Noordam, R and Caulfield, MJ and Jukema, JW and Worrall, BB and Munroe, PB and Menon, U and Power, C and Kuh, D and Lawlor, DA and Humphries, SE and Mook-Kanamori, DO and Sattar, N and Kivimaki, M and Price, JF and Davey Smith, G and Dudbridge, F and Hingorani, AD and Holmes, MV and Casas, JP (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). 2373 - 2388. ISSN 0009-7322

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Abstract

© 2017 American Heart Association, Inc. 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/m 2 ; 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: Article
Subjects: H Social Sciences > H Social Sciences (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Jim Jamieson
Date Deposited: 21 Jul 2017 10:54
Last Modified: 17 Aug 2017 17:15
URI: http://repository.essex.ac.uk/id/eprint/20087

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