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

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

In: Circulation, Vol. 135, No. 24, 13.06.2017, p. 2373-2388.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Dale, C, Fatemifar, G, Palmer, T, White, J, Prieto-Merino, D, Zabaneh, D, Engmann, JEL, Shah, T, Wong, A, Warren, HR, McLachlan, S, Trompet, S, Moldovan, M, Morris, RW, Sofat, R, Kumari, M, Hyppönen, E, Jefferis, BJ, Gaunt, TR, Ben-Shlomo, Y, Zhou, A, Gentry-Maharaj, A, Ryan, A, de Mutsert, R, Noordam, R, Caulfield, MJ, Jukema, JW, Worrall, BB, Munroe, PB, Menon, U, Power, C, Kuh, D, Lawlor, DA, Humphries, SE, Mook-Kanamori, DO, Davey Smith, G, Sattar, N, Kivimaki, M, Price, JF, Dudbridge, F, Hingorani, AD, Holmes, MV & Casas, J-P 2017, 'Causal Associations of Adiposity and Body Fat Distribution with Coronary Heart Disease, Stroke Subtypes and Type 2 Diabetes: A Mendelian randomization analysis', Circulation, vol. 135, no. 24, pp. 2373-2388. https://doi.org/10.1161/CIRCULATIONAHA.116.026560

APA

Dale, C., Fatemifar, G., Palmer, T., 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., ... Casas, J-P. (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), 2373-2388. https://doi.org/10.1161/CIRCULATIONAHA.116.026560

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Author

Dale, Caroline ; Fatemifar, Ghazaleh ; Palmer, Tom ; White, Jonathan ; Prieto-Merino, David ; Zabaneh, Delilah ; Engmann, Jorgen E. L. ; Shah, Tina ; Wong, Andrew ; Warren, Helen R. ; McLachlan, Stela ; Trompet, Stella ; Moldovan, Max ; Morris, Richard W. ; Sofat, Reecha ; Kumari, Meena ; Hyppönen, Elina ; Jefferis, Barbara J. ; Gaunt, Tom R. ; Ben-Shlomo, Yoav ; Zhou, Ang ; Gentry-Maharaj, Aleksandra ; Ryan, Andy ; de Mutsert, Renée ; Noordam, Raymond ; Caulfield, Mark J. ; Jukema, J. Wouter ; Worrall, Bradford B. ; Munroe, Patricia B. ; Menon, Usha ; Power, Chris ; Kuh, Diana ; Lawlor, Debbie A. ; Humphries, Steve E. ; Mook-Kanamori, Dennis O. ; Davey Smith, George ; Sattar, Naveed ; Kivimaki, Mika ; Price, Jacqueline F. ; Dudbridge, Frank ; Hingorani, Aroon D. ; Holmes, Michael V. ; Casas, Juan-Pablo. / Causal Associations of Adiposity and Body Fat Distribution with Coronary Heart Disease, Stroke Subtypes and Type 2 Diabetes : A Mendelian randomization analysis. In: Circulation. 2017 ; Vol. 135, No. 24. pp. 2373-2388.

Bibtex

@article{8234eb46080943908de741933c89f57f,
title = "Causal Associations of Adiposity and Body Fat Distribution with Coronary Heart Disease, Stroke Subtypes and Type 2 Diabetes: A Mendelian randomization analysis",
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.",
author = "Caroline Dale and Ghazaleh Fatemifar and Tom Palmer and Jonathan White and David Prieto-Merino and Delilah Zabaneh and Engmann, {Jorgen E. L.} and Tina Shah and Andrew Wong and Warren, {Helen R.} and Stela McLachlan and Stella Trompet and Max Moldovan and Morris, {Richard W.} and Reecha Sofat and Meena Kumari and Elina Hypp{\"o}nen and Jefferis, {Barbara J.} and Gaunt, {Tom R.} and Yoav Ben-Shlomo and Ang Zhou and Aleksandra Gentry-Maharaj and Andy Ryan and {de Mutsert}, Ren{\'e}e and Raymond Noordam and Caulfield, {Mark J.} and Jukema, {J. Wouter} and Worrall, {Bradford B.} and Munroe, {Patricia B.} and Usha Menon and Chris Power and Diana Kuh and Lawlor, {Debbie A.} and Humphries, {Steve E.} and Mook-Kanamori, {Dennis O.} and {Davey Smith}, George and Naveed Sattar and Mika Kivimaki and Price, {Jacqueline F.} and Frank Dudbridge and Hingorani, {Aroon D.} and Holmes, {Michael V.} and Juan-Pablo Casas",
note = "{\textcopyright}2017 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited",
year = "2017",
month = jun,
day = "13",
doi = "10.1161/CIRCULATIONAHA.116.026560",
language = "English",
volume = "135",
pages = "2373--2388",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "24",

}

RIS

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 -