Journal
OBESITY
Volume 26, Issue 11, Pages 1796-1806Publisher
WILEY
DOI: 10.1002/oby.22313
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Funding
- Cancer Research UK programme [C18281/A19169]
- Medical Research Council Integrative Epidemiology Unit (MRC IEU) [MC_UU_12013/1-6, MC_UU_00011/1-7]
- MRC-IEU [MC_UU_12013/3, MC_UU_12013/4, MC_UU_12013/9, MC_UU_12013/1, MC_UU_00011/1]
- Wellcome Trust [202802/Z/16/Z]
- MRC [MC_UU_12013/1, MC_UU_12013/3, MC_UU_12013/4, MC_UU_12013/9, MC_PC_12028] Funding Source: UKRI
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ObjectiveMethodsThe aim of this study was to obtain estimates of the causal relationship between BMI and mortality. 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. ResultsConclusionsMR analyses supported a causal association between higher BMI and greater risk of all-cause mortality (hazard ratio [HR] per 1 kg/m(2): 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. 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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