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Publication - Professor Tom Gaunt

    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, Fatemifar, G, Palmer, TM, 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, T, Ben-Shlomo, Y, Zhou, A, Gentry-Maharaj, A, Ryan, A, , , Mutsert, Rd, Noordam, R, Caulfield, MJ, Jukema, JW, Worrall, B, Munroe, PB, Menon, U, Power, C, Kuh, DJL, Lawlor, DA, Humphries, SE, Mook-Kanamori, DO, Smith, GD, Sattar, N, Kivimaki, MJ & others 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, vol 135., pp. 2373-2388


    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 we find OR 1.82 (95%CI 1.38-2.42) per 1SD WHRadjBMI and OR 1.98 (95%CI 1.41-2.78) per 1SD BMI. Both WHRadjBMI and BMI were associated with increased left ventricular hypertrophy, glycaemic traits, interleukin-6, and circulating lipids. WHRadjBMI was associated with carotid intima-media thickness (37%; 95%CI: 7%-74% 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 adiposity burden on health should include measures of central and general adiposity.

    Full details in the University publications repository