Genetically predicted basal metabolic rate and infectious diseases: a Mendelian randomization study

Abstract Background The causal relationship between basal metabolic rate (BMR) and infectious diseases remains elusive. This study aims to clarify this association. Methods This study analyzed genome-wide association studies (GWASs) data from the UK Biobank and FinnGen cohorts to investigate the association between BMR and infectious diseases in European populations. Mendelian randomization (MR) analysis was initially employed, followed by multivariable Mendelian randomization (MVMR) to account for potential confounders. Mediation analysis further confirmed significant relationships. Sensitivity analyses were conducted to validate the study findings. Results Using two sample MR, genetically predicted BMR was positively linked to skin and soft tissue infections (SSTIs) (OR: 1.31, 95% CI: 1.18–1.47, P < .001), osteomyelitis (OR: 1.95, 95% CI: 1.36–2.80, P < .001) (1.36 ± 2.80), all-cause infections (OR: 1.36, 95% CI: 1.26–1.48, P < .001) and sepsis (OR: 1.36, 95% CI: 1.23–1.51, P < .001). MVMR analysis confirmed BMR's direct causal effect on SSTIs, osteomyelitis, all-cause infections, and sepsis, except for BMI and other factors affecting osteomyelitis. Mediation analysis revealed VAT as a mediator in the linkage between BMR and SSTIs and all-cause infections. HbA1c mediated the path from BMR to osteomyelitis, while CRP and BMI exhibited mediation effects in the BMR-all-cause infections relationship. Conclusion The study revealed a significant link between increased BMR and elevated risks of SSTIs, osteomyelitis, and bacterial infections, highlighting the intricate BMR-immune connection and its implications for disease control. Key message What is already known on this topic: High BMR is positively correlated with COVID-19 and associated with proinflammatory and immunological activation, but the relationship between BMR and other infectious diseases remains largely unexplored. What this study adds: Higher BMR significantly raises the risk of SSTIs, osteomyelitis, all-cause infections, and sepsis. VAT, HbA1c, CRP, and BMI may mediate the BMR-infection relationship. How this study might affect research, practice, or policy: A higher BMR may be a valuable indicator associated with an increased risk for SSTIs, osteomyelitis, and sepsis. Modulating BMR might hold promise as a clinically relevant intervention to prevent specific infectious diseases.