Exploration of the causal relationship between obesity and sepsis and investigation of the mechanism of anoikis in sepsis

Objective To explore the causal relationship between common obesity indicators (body mass index, hip circumference, waist circumference) and sepsis based on Mendelian randomization analysis. Furthermore, the mechanism of the role of anoikis in sepsis was explored based on the bioinformatics mining. Methods In the first part, SNPs strongly associated with body mass index, Hip circumference, and Waist circumference were downloaded from the genome-wide association study(GWAS) database and screened as instrumental variables, and sepsis was used as an outcome variable. IVW was used as the primary analysis method to assess causal associations, with Weighted median and Mr-Egger as complementary methods. Heterogeneity among genetic variants was detected using Cochran's Q test and funnel plot analysis, horizontal pleiotropy was detected using Mr-Egger-intercept, and sensitivity analyses were performed using the "leave-one-out" method. In the second part, the biological functions and mechanisms of anoikis in sepsis were investigated based on R-analysis downloaded from the GEO database. Resuts The body mass index(BMI), hip circumference(HC), and waist circumference (WC) were risk factors for sepsis. The core ARDEGs SERPINB1, MERTK and CEACAM8 were significantly up-regulated in sepsis and showed good diagnostic efficacy. The risk model based on ARDEGs showed good potential for clinical application. SERPINB1 may be involved in the regulation of inflammatory responses in sepsis through the NLRC4/CASP1-inflammatory effects signaling pathway. Conclusion There is a causal association between obesity and sepsis and obesity is a risk factor for sepsis. The anoikis genes SERPINB1, MERTK and CEACAM8 are potential diagnostic targets for sepsis. And SERPINB1 may be involved in the regulation of inflammatory effects in sepsis through the NLRC4/CASP1- inflammatory effects signaling pathway.