BMI and Mortality in UK Biobank: Revised Estimates Using Mendelian Randomization

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Abstract

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.
Original languageEnglish
Pages (from-to)1796-1806
Number of pages11
JournalObesity
Volume26
Issue number11
Early online date25 Oct 2018
DOIs
Publication statusPublished - Nov 2018

Structured keywords

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  • Projects

    IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

    Gaunt, L. F. & Davey Smith, G.

    1/04/1831/03/23

    Project: Research

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