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

Area of Science:

• Genetics and Epidemiology
• Public Health
• Cardiovascular Research

Background:

• The relationship between Body Mass Index (BMI) and mortality is complex, with observational studies suggesting a J-shaped association.
• Establishing a causal link between BMI and mortality is crucial for public health interventions and clinical guidelines.

Purpose of the Study:

• To estimate the causal relationship between BMI and all-cause and cause-specific mortality.
• To investigate the causal effect of BMI on mortality using genetic variation associated with BMI.

Main Methods:

• Mendelian randomization (MR) analysis was employed using BMI-associated genotypic variation.
• Data from UK Biobank participants of White British ancestry were analyzed.
• Cause-specific mortality analyses included cardiovascular diseases, cancers, and respiratory diseases.

Main Results:

• MR analyses supported a causal association between higher BMI and increased risk of all-cause mortality (HR per 1 kg/m²: 1.03).
• Higher BMI was causally linked to increased mortality from cardiovascular diseases, coronary heart disease, and specific cancer types.
• A decreased risk of lung cancer mortality was observed, and sex-specific effects were noted for bladder and respiratory disease mortality.

Conclusions:

• Results confirm a causal role of higher BMI in elevating the risk of all-cause mortality.
• Higher BMI is causally associated with increased mortality from several specific causes, including cardiovascular diseases.