Elevated body mass index is associated with an increased risk of infectious disease admissions and mortality: a mendelian randomization study

Objective: The effect of body mass index (BMI) on the risk of infectious diseases admissions and mortality is unclear and is difficult to study given the risks of confounding variables.

Methods: We used genome-wide association studies (GWASs) with mendelian randomization (MR) to obtain causal inference of BMI on the following infectious diseases outcomes: hospital admissions for pneumonia, sepsis, urinary tract infections, skin and soft tissue infections (SSTIs) or all-cause infections. For patients with pneumonia and sepsis, we also analysed their 28-day and 90-day mortalities. The UK Biobank (UKB) cohort (n > 500 000) provided data for GWASs on infectious diseases. The GIANT consortium (n = 681 265) GWAS was used to identify single-nucleotide polymorphisms (SNPs) associated with BMI.

Results: Genetically increased BMI, by one standard deviation, was associated with higher rates of admission due to all infectious disease. The effect was most important for SSTIs (OR: 1.11, 95%CI: 1.09, 1.12). Increasing BMI by one standard deviation was associated with higher pneumonia mortality, especially at 28 days (OR: 1.03, 95%CI: 1.01, 1.05). BMI was not clearly associated with sepsis mortality, although interpretation of the results was limited by a small sample size. There were consistent findings in sensitivity analysis performed by removing highly pleiotropic SNPs and multivariate MR including type-2 diabetes mellitus, estimated glomerular filtration rate, high-density lipoprotein, educational attainment, and a history of smoking.

Conclusions: Increased BMI was associated with increased risk of admission for infectious disease and mortality. While the pathophysiology behind this phenomenon remains unknown, increasing BMI may influence immune dysregulation.