Abstract: BACKGROUND: Conventional observational studies are inadequate to reveal the potential causal relationship of biomarkers in burns patients. Mendelian randomization, leveraging genetic variation as an instrumental variable to mimic the advantages of randomized controlled trials, has emerged as a crucial tool for dissecting causal associations in complex diseases.
OBJECTIVE: To explore the relationship of burn injury with 41 inflammatory cytokines and 35 blood and urinary biomarkers using Mendelian Randomization. 
METHODS: (1) Burn-related data of genome-wide association studies were obtained from the IEU open GWAS project database, constructed by The University of Bristol, UK, including 218 131 samples and 16 380 465 single nucleotide polymorphisms were included in the study. (2) Data for 41 types of inflammatory cytokines were derived from a study involving 8 293 participants in the Finnish Young Cardiovascular Risk Study database, which is constructed by the Research Centre for Applied and Preventive Cardiovascular Medicine, University of Turku. (3) Data for 35 types of blood and urinary biomarkers were derived from a study involving 363 228 participants from the UK Biobank, which is a large biomedical database project jointly initiated by the UK government, the Wellcome Trust, and the Medical Research Council of the UK. Single nucleotide polymorphisms were employed as instrumental variables, and analyses were conducted using inverse variance weighted, Mendelian Randomization-Egger, weighted median, and weighted mode methods. Heterogeneity of results was assessed via Cochrane’s Q test. The reliability of exposure-outcome associations was evaluated using Mendelian Randomization-Egger intercept tests, Mendelian Randomization-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out sensitivity analyses. 
RESULTS AND CONCLUSION: The levels of interleukin-9 (odds ratio=0.97; 95% confidence interval, 0.949 to 0.997; P=0.030) and testosterone (odds ratio=0.997; 95% confidence interval, 0.995 to 0.999; P=0.025) were reduced in burn patients. No heterogeneity or horizontal pleiotropy demonstrated the robustness of the results. Through Mendelian randomization analysis, the study revealed the reduced interleukin-9 and testosterone levels following burns, suggesting that elevating these could potentially facilitate tissue repair and mitigate protein catabolism.

Key words: burn, inflammatory factors, biomarkers, Mendelian randomization, interleukin-9, testosterone