Rights statement: ©2017 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Causal Associations of Adiposity and Body Fat Distribution with Coronary Heart Disease, Stroke Subtypes and Type 2 Diabetes
T2 - A Mendelian randomization analysis
AU - Dale, Caroline
AU - Fatemifar, Ghazaleh
AU - Palmer, Tom
AU - White, Jonathan
AU - Prieto-Merino, David
AU - Zabaneh, Delilah
AU - Engmann, Jorgen E. L.
AU - Shah, Tina
AU - Wong, Andrew
AU - Warren, Helen R.
AU - McLachlan, Stela
AU - Trompet, Stella
AU - Moldovan, Max
AU - Morris, Richard W.
AU - Sofat, Reecha
AU - Kumari, Meena
AU - Hyppönen, Elina
AU - Jefferis, Barbara J.
AU - Gaunt, Tom R.
AU - Ben-Shlomo, Yoav
AU - Zhou, Ang
AU - Gentry-Maharaj, Aleksandra
AU - Ryan, Andy
AU - de Mutsert, Renée
AU - Noordam, Raymond
AU - Caulfield, Mark J.
AU - Jukema, J. Wouter
AU - Worrall, Bradford B.
AU - Munroe, Patricia B.
AU - Menon, Usha
AU - Power, Chris
AU - Kuh, Diana
AU - Lawlor, Debbie A.
AU - Humphries, Steve E.
AU - Mook-Kanamori, Dennis O.
AU - Davey Smith, George
AU - Sattar, Naveed
AU - Kivimaki, Mika
AU - Price, Jacqueline F.
AU - Dudbridge, Frank
AU - Hingorani, Aroon D.
AU - Holmes, Michael V.
AU - Casas, Juan-Pablo
N1 - ©2017 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited
PY - 2017/6/13
Y1 - 2017/6/13
N2 - 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.
AB - 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.
U2 - 10.1161/CIRCULATIONAHA.116.026560
DO - 10.1161/CIRCULATIONAHA.116.026560
M3 - Journal article
VL - 135
SP - 2373
EP - 2388
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 24
ER -