Abstract
Objective Obtain estimates of the causal relationship between different levels of body mass index (BMI) and mortality.
Methods Mendelian randomization (MR) was conducted using genotypic variation reliably associated with BMI to test the causal effect of increasing BMI on all-cause and cause-specific mortality in participants of White British ancestry in UK Biobank.
Results MR analyses supported existing evidence for a causal association between higher levels of BMI and greater risk of all-cause mortality (hazard ratio (HR) per 1kg/m2: 1.02; 95% CI: 0.97,1.06) and mortality from cardiovascular diseases (HR: 1.12; 95% CI: 1.02, 1.23), specifically coronary heart disease (HR: 1.19; 95% CI: 1.05, 1.35) and those other than stroke/aortic aneurysm (HR: 1.13; 95% CI: 0.93, 1.38), stomach cancer (HR: 1.30; 95% CI: 0.91, 1.86) and oesophageal cancer (HR: 1.08; 95% CI: 0.84, 1.38), and with decreased risk of lung cancer mortality (HR: 0.97; 95% CI: 0.84, 1.11). Sex-stratified analyses supported a causal role of higher BMI in increasing the risk of mortality from bladder cancer in males and other causes in females, but in decreasing the risk of respiratory disease mortality in males. The characteristic J-shaped observational association between BMI and mortality was visible with MR analyses but with a smaller value of BMI at which mortality risk was lowest and apparently flatter over a larger range of BMI.
Conclusion Results support a causal role of higher BMI in increasing the risk of all-cause mortality and mortality from other causes. However, studies with greater numbers of deaths are needed to confirm the current findings.
Footnotes
Funding: NJT is a Wellcome Trust Investigator (202802/Z/16/Z), a programme lead in the MRC Integrative Epidemiology Unit (MRC-IEU; MC_UU_12013/3), a work-package lead in the Integrative Cancer Epidemiology Programme (ICEP) that is supported by a Cancer Research UK programme grant (C18281/A19169) and works within the University of Bristol NIHR Biomedical Research Centre (BRC). GDS is the director and a programme lead in the MRC-IEU (MC_UU_12013/1). KHW is funded equally by two programs of the MRC-IEU (MC_UU_12013/3 and MC_UU_12013/4). DC is funded by the statistics theme of the MRC-IEU (MC_UU_12013/9) and is also affiliated to program 1 (MC_UU_12013/1). The funders of the study had no role in the study design, data collection, data analysis, data interpretation or writing of the report.
Disclosures: NS is a member of the UK Biobank international scientific advisory board and enhancements committee. This had no bearing on the study. Otherwise, the authors declared no conflicts of interest.