BMI and mortality in UK Biobank: revised estimates using Mendelian randomization

Wade, K. H., Carslake, D., Sattar, N. , Davey Smith, G. and Timpson, N. J. (2018) BMI and mortality in UK Biobank: revised estimates using Mendelian randomization. Obesity, 26(11), pp. 1796-1806. (doi: 10.1002/oby.22313) (PMID:30358150)

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Objective: The aim of this study was to obtain estimates of the causal relationship between BMI and mortality. Methods: Mendelian randomization (MR) with BMI‐associated genotypic variation was used to test the causal effect of BMI on all‐cause and cause‐specific mortality in UK Biobank participants of White British ancestry. Results: MR analyses supported a causal association between higher BMI and greater risk of all‐cause mortality (hazard ratio [HR] per 1 kg/m2: 1.03; 95% CI: 0.99‐1.07) and mortality from cardiovascular diseases (HR: 1.10; 95% CI: 1.01‐1.19), specifically coronary heart disease (HR: 1.12; 95% CI: 1.00‐1.25) and those excluding coronary heart disease/stroke/aortic aneurysm (HR: 1.24; 95% CI: 1.03‐1.48), stomach cancer (HR: 1.18; 95% CI: 0.87‐1.62), and esophageal cancer (HR: 1.22; 95% CI: 0.98‐1.53), and a decreased risk of lung cancer mortality (HR: 0.96; 95% CI: 0.85‐1.08). Sex stratification supported the causal role of higher BMI increasing bladder cancer mortality risk (males) but decreasing respiratory disease mortality risk (males). The J‐shaped observational association between BMI and mortality was visible with MR analyses, but the BMI at which mortality was minimized was lower and the association was flatter over a larger BMI range. Conclusions: Results support a causal role of higher BMI in increasing the risk of all‐cause mortality and mortality from several specific causes.

Item Type:Articles
Additional Information:NJT is a Wellcome Trust Investigator (202802/Z/16/Z) and a work‐package lead in the Integrative Cancer Epidemiology Programme that is supported by a Cancer Research UK programme grant (C18281/A19169), and he works within the University of Bristol National Institute for Health Research Biomedical Research Centre. GDS is the director and a programme lead in the Medical Research Council Integrative Epidemiology Unit (MRC IEU) (grant codes for 2013‐2018: MC_UU_12013/1‐6 and for 2018‐2023: MC_UU_00011/1‐7). At the start of this project, KHW was funded equally by two programs of the MRC‐IEU (grant codes for 2013‐2018: MC_UU_12013/3 and MC_UU_12013/4) and is now funded by the Wellcome Trust Investigator award (202802/Z/16/Z, PI: NJT). At the start of this project, DC was funded by the statistics theme of the MRC‐IEU (grant code for 2013‐2018: MC_UU_12013/9) and is now affiliated to program 1 of the MRC‐IEU (grant code for 2013‐2018: MC_UU_12013/1 and for 2018‐2023: MC_UU_00011/1).
Glasgow Author(s) Enlighten ID:Sattar, Professor Naveed
Authors: Wade, K. H., Carslake, D., Sattar, N., Davey Smith, G., and Timpson, N. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Obesity
ISSN (Online):1930-739X
Published Online:25 October 2018
Copyright Holders:Copyright © 2018 The Obesity Society
First Published:First published in Obesity 26(11): 1796-1806
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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