Dataset Information

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

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.

SUBMITTER: Wade KH

PROVIDER: S-EPMC6334168 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Wade Kaitlin H KH Carslake David D Sattar Naveed N Davey Smith George G Timpson Nicholas J NJ

Obesity (Silver Spring, Md.) 20181101 11

<h4>Objective</h4>The aim of this study was to obtain estimates of the causal relationship between BMI and mortality.<h4>Methods</h4>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.<h4>Results</h4>MR analyses supported a causal association between higher BMI and greater risk of all-cause mortality (hazard ratio [HR] per 1 kg/m<sup>2</sup> : ...[more]

PMID: 30358150

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Project description:Observational studies suggest alcohol use promotes the development of some adverse cardiometabolic traits but protects against others including outcomes related to coronary artery disease. We used Mendelian randomization (MR) to explore causal relationships between the degree of alcohol consumption and several cardiometabolic traits in the UK Biobank. Using the well-established ADH1B Arg47His variant (rs1229984) and up to 24 additional SNPs recently found to be associated with alcohol consumption in an independent dataset as instruments, we conducted two-stage least squares and inverse weighted variance MR analyses, both as one-sample analyses in the UK Biobank and as two-sample analyses in external consortia. In the UK Biobank inverse variance weighted analyses, we found that one additional drink of alcohol per day was positively associated with systolic blood pressure (beta = 2.65 mmHg [1.40, 3.89]), hemorrhagic stroke (OR = 2.25 [1.41, 3.60]), and atrial fibrillation (OR = 1.26 [1.07, 1.48]), which were replicated in multivariable analyses. Alcohol was also associated with all cardiovascular disease and all-cause death. A positive association with myocardial infarction did not replicate in multivariable analysis, with suggestive mediation through blood pressure; similarly, a positive association between alcohol use with type 2 diabetes was mitigated by BMI in multivariable analysis. Findings were generally null in replication with two-sample analyses. Alcohol was not protective for any disease outcome with any analysis method, dataset, or strata. Stratifications by sex and smoking in the UK Biobank revealed higher point estimates of risk for several outcomes for men and mixed results for smoking strata, but no statistically significant heterogeneity. Our results are consistent with an overall harmful and/or null effect of alcohol on cardiometabolic health at all levels of use and suggest that even moderate alcohol use should not be promoted as a part of a healthy diet and lifestyle.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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