G Butler-Laporte1, A Harroud2, V Forgetta3, J B Richards4. 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.
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.
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 pneumoniamortality, especially at 28 days (OR: 1.03, 95%CI: 1.01, 1.05). BMI was not clearly associated with sepsismortality, 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.
Authors: Tormod Rogne; Kristin V Liyanarachi; Humaira Rasheed; Laurent F Thomas; Helene M Flatby; Jørgen Stenvik; Mari Løset; Dipender Gill; Stephen Burgess; Cristen J Willer; Kristian Hveem; Bjørn O Åsvold; Ben M Brumpton; Andrew T DeWan; Erik Solligård; Jan K Damås Journal: J Invest Dermatol Date: 2021-03-01 Impact factor: 7.590