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

G Butler-Laporte; A Harroud; V Forgetta; J B Richards

doi:10.1016/j.cmi.2020.06.014

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

Clin Microbiol Infect. 2020 Jun 24:S1198-743X(20)30356-6. doi: 10.1016/j.cmi.2020.06.014. Online ahead of print.

Authors

G Butler-Laporte¹, A Harroud², V Forgetta³, J B Richards⁴

Affiliations

¹ Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada; Division of Infectious Diseases and Medical Microbiology, McGill University, Montréal, Québec, Canada. Electronic address: guillaume.butler-laporte@mail.mcgill.ca.
² Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
³ Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada.
⁴ Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada; Department of Human Genetics, McGill University, Montréal, Québec, Canada; Department of Twin Research, King's College London, London, UK. Electronic address: brent.richards@mcgill.ca.

PMID: 32592749
DOI: 10.1016/j.cmi.2020.06.014

Abstract

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.

Keywords: Body mass index; Infections; Mendelian randomization; Mortality; Obesity; Sepsis.

Abstract

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