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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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  • Caroline Dale
  • Ghazaleh Fatemifar
  • Jonathan White
  • David Prieto-Merino
  • Delilah Zabaneh
  • Jorgen E. L. Engmann
  • Tina Shah
  • Andrew Wong
  • Helen R. Warren
  • Stela McLachlan
  • Stella Trompet
  • Max Moldovan
  • Richard W. Morris
  • Reecha Sofat
  • Meena Kumari
  • Elina Hyppönen
  • Barbara J. Jefferis
  • Tom R. Gaunt
  • Yoav Ben-Shlomo
  • Ang Zhou
  • Aleksandra Gentry-Maharaj
  • Andy Ryan
  • Renée de Mutsert
  • Raymond Noordam
  • Mark J. Caulfield
  • J. Wouter Jukema
  • Bradford B. Worrall
  • Patricia B. Munroe
  • Usha Menon
  • Chris Power
  • Diana Kuh
  • Debbie A. Lawlor
  • Steve E. Humphries
  • Dennis O. Mook-Kanamori
  • George Davey Smith
  • Naveed Sattar
  • Mika Kivimaki
  • Jacqueline F. Price
  • Frank Dudbridge
  • Aroon D. Hingorani
  • Michael V. Holmes
  • Juan-Pablo Casas
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<mark>Journal publication date</mark>13/06/2017
<mark>Journal</mark>Circulation
Issue number24
Volume135
Number of pages16
Pages (from-to)2373-2388
Publication StatusPublished
Early online date12/05/17
<mark>Original language</mark>English

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.

Bibliographic note

©2017 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited