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

Dale, Caroline and Fatemifar, Ghazaleh and Palmer, Tom and White, Jonathan and Prieto-Merino, David and Zabaneh, Delilah and Engmann, Jorgen E. L. and Shah, Tina and Wong, Andrew and Warren, Helen R. and McLachlan, Stela and Trompet, Stella and Moldovan, Max and Morris, Richard W. and Sofat, Reecha and Kumari, Meena and Hyppönen, Elina and Jefferis, Barbara J. and Gaunt, Tom R. and Ben-Shlomo, Yoav and Zhou, Ang and Gentry-Maharaj, Aleksandra and Ryan, Andy and de Mutsert, Renée and Noordam, Raymond and Caulfield, Mark J. and Jukema, J. Wouter and Worrall, Bradford B. and Munroe, Patricia B. and Menon, Usha and Power, Chris and Kuh, Diana and Lawlor, Debbie A. and Humphries, Steve E. and Mook-Kanamori, Dennis O. and Davey Smith, George and Sattar, Naveed and Kivimaki, Mika and Price, Jacqueline F. and Dudbridge, Frank and Hingorani, Aroon D. and Holmes, Michael V. and Casas, Juan-Pablo (2017) Causal Associations of Adiposity and Body Fat Distribution with Coronary Heart Disease, Stroke Subtypes and Type 2 Diabetes:A Mendelian randomization analysis. Circulation, 135 (24). pp. 2373-2388. ISSN 0009-7322

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Abstract

Background—Implications of different adiposity measures on cardiovascular disease aetiology remain unclear. In this paper we quantify and contrast causal associations of central adiposity (waist:hip ratio adjusted for BMI (WHRadjBMI)) and general adiposity (body mass index (BMI)) with cardiometabolic disease. Methods—97 independent single nucleotide polymorphisms (SNPs) for BMI and 49 SNPs for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with CHD data from CARDIoGRAMplusC4D (combined total 66,842 cases), stroke from METASTROKE (12,389 ischaemic stroke cases), type 2 diabetes (T2D) from DIAGRAM (34,840 cases), and lipids from GLGC (213,500 participants) consortia. Primary outcomes were CHD, T2D, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Results—Each one standard deviation (SD) higher WHRadjBMI (1SD~0.08 units) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD: 1.48; 95%CI: 1.28-1.71), similar to findings for BMI (1SD~4.6kg/m2; OR for CHD: 1.36; 95%CI: 1.22-1.52). Only WHRadjBMI increased risk of ischaemic stroke (OR 1.32; 95%CI 1.03-1.70). For T2D, 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 1SD higher WHRadjBMI and BMI respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycaemic traits, interleukin-6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95%CI: 9%-77% per 1SD). Conclusions—Both general and central adiposity have causal effects on CHD and T2D. 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:
Journal Article
Journal or Publication Title:
Circulation
Additional Information:
©2017 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2737
Subjects:
ID Code:
85875
Deposited By:
Deposited On:
07 Apr 2017 15:42
Refereed?:
Yes
Published?:
Published
Last Modified:
22 Sep 2020 03:14