Research Paper Volume 15, Issue 15 pp 7727—7740

Figure 1. Description of the study design in this MR study. Study design consists of three parts: forward analysis (sepsis to LTL), reverse analysis (LTL to sepsis) and one-way analysis (LTL to septic 28-day death). In the population cohort of exposure factor we obtain SNPs (consistent with Exclusivity and Independence assumptions), and according to the Correlation assumption, we obtain SNPs of exposure factors. In another cohort of outcome event, we obtain SNPs, and we can extract outcome-related SNPs by matching with SNPs of exposure factor. Correlation between SNPs in both groups is analyzed, then correctness of causal pathway is judged. Three types of MR analysis correspond to the judgment of three causal pathways: Causal Pathway 1, people with sepsis have a tendency to shortening leukocyte telomeres; Causal Pathway 2, people with shorter LTL increase the susceptibility to sepsis; Causal Pathway 3, people with shorter LTL are more likely to die of sepsis within 28 days. The blue represents the phenotypes and SNPs involving in sepsis and 28-day death. The pink represents phenotypes and SNPs of LTL. The red illustrates threshold conditions of genetic instrumental variables. Yellow, green, and red balls represent the core assumptions of MR analysis. Abbreviations: LTL: leukocyte telomere length; SNPs: single nucleotide polymorphisms.