Iron status and the risk of sepsis and severe COVID-19: a two-sample Mendelian randomization study

publishedVersio

Iron status and the risk of sepsis and severe COVID-19: a two-sample Mendelian randomization study

Observational studies have indicated an association between iron status and risk of sepsis and COVID-19. We estimated the effect of genetically-predicted iron biomarkers on risk of sepsis and risk of being hospitalized with COVID-19, performing a two-sample Mendelian randomization study. For risk of sepsis, one standard deviation increase in genetically-predicted serum iron was associated with odds ratio (OR) of 1.14 (95% confidence interval [CI] 1.01–1.29, P = 0.031). The findings were supported in the analyses for transferrin saturation and total iron binding capacity, while the estimate for ferritin was inconclusive. We found a tendency of higher risk of hospitalization with COVID-19 for serum iron; OR 1.29 (CI 0.97–1.72, P = 0.08), whereas sex-stratified analyses showed OR 1.63 (CI 0.94–2.86, P = 0.09) for women and OR 1.21 (CI 0.92–1.62, P = 0.17) for men. Sensitivity analyses supported the main findings and did not suggest bias due to pleiotropy. Our findings suggest a causal effect of genetically-predicted higher iron status and risk of hospitalization due to sepsis and indications of an increased risk of being hospitalized with COVID-19. These findings warrant further studies to assess iron status in relation to severe infections, including the potential of improved management

Risk of lower respiratory tract infections: a genome-wide association study with Mendelian randomization analysis in three independent European populations

Objective: Lower respiratory tract infections (LRTIs) are a leading cause of morbidity and mortality worldwide. Few studies have previously investigated the genetic susceptibility and potential risk factors for LRTI. Methods: We used data from UK Biobank, HUNT, and FinnGen, to conduct a genome-wide association study (GWAS). Cases were subjects hospitalized with LRTI, and controls were subjects with no such hospitalization. We conducted stratification and interaction analyses to evaluate if the genetic effect of LRTI differed by sex or smoking. Mendelian randomization [MR] analyses were conducted to identify the unconfounded relationship between cardiometabolic risk factors and LRTI. Results: A total of 25,320 cases and 575,294 controls were included. The 15q25.1 locus reached genome-wide significance in the meta-analysis (rs10519203: OR = 0.94, P = 3.87e-11). The protective effect of effect allele of rs10519203 was present among smokers (OR = 0.90 [95% CI = 0.87 - 0.92, P = 1.38e-15]) but not among never-smokers (OR = 1.01 [95% CI = 0.97 - 1.06, P = 5.20e-01]). In MR analyses, we found that increasing body mass index (OR = 1.31 [95% CI = 1.24 - 1.40, P = 3.78e-18]), lifetime smoking (OR = 2.83 [95% CI = 2.34 - 3.42, P = 6.56e-27]), and systolic blood pressure robustly increased the risk of LRTIs (OR = 1.11 [95% CI = 1.02 - 1.22, P = 1.48e-02]). Conclusion: A region in 15q25.1 was strongly associated with LRTI susceptibility. Reduction of the prevalence of smoking, overweight, obesity, and hypertension may reduce the disease burden of LRTIs. Keywords: body mass index, genome-wide association study, lowerrespiratory tract infection, mendelianrandomization, pneumonia, respiratory infection, smokin