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Obesity (Silver Spring). 2018 Nov;26(11):1796-1806. doi: 10.1002/oby.22313.

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

Author information

1
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
2
Population Health Sciences, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK.
3
Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.

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.

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