The effect of body-mass index (BMI) on the risk of infectious diseases admissions and mortality is unclear and is difficult to study given risks of confounding variables.
We used genome-wide association studies (GWAS) with mendelian randomisation (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 (SSTI) or all-cause infections. For patients with pneumonia and sepsis, we also analyzed their 28-day and 90-day mortality. 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 BMI.
Genetically increased BMI, by one standard deviation, was associated with higher rates of admissions due to all infectious disease. The effect was most important for SSTI (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, though results were limited by a small sample size. Consistent findings were found 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.
Increased BMI was associated with increased risks of admission for infectious disease and mortality. While the pathophysiology behind this phenomenon remains unknown, increasing BMI may influence immune dysregulation.

Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.