Sarcopenia-associated traits and sepsis risk: a Mendelian Randomization and Prospective Observational Study

BACKGROUND: Sarcopenia is closely associated with increased mortality in sepsis patients. However, the relationship between sarcopenia and sepsis incidence remains unclear. This study employed Mendelian randomization (MR) and prospective observational analysis to investigates the potential causal links between sarcopenia and sepsis risk. METHODS: MR analysis incorporated nine GWAS datasets of sarcopenia-associated traits (muscle strength, muscle quantity, and physical performance) and one sepsis GWAS dataset. A prospective observational study was conducted between June, 2024 and March, 2025. Five ultrasound-derived muscle quantity indices [ thickness of the rectus femoris (RF-TH), vastus intermedius (VI-TH) and quadriceps femoris (QF-TH), cross-sectional area of the rectus femoris (RF-CSA), thickness of the tibialis anterior (TA-TH)] and one muscle quality index (tibialis anterior pennation angle, TA-PA) were assessed on the first day after ICU admission. The outcome event was sepsis incidence during ICU stay. Patients were categorized into non-sepsis group (n=135), and sepsis group (n=37). Logistic regression was conducted to identify risk factors associated with sepsis incidence during ICU stay. RESULTS: MR analysis indicated that physical performance assessed by usual walking pace was significantly associated with a reduced risk of sepsis among three traits (OR: 0.29, 95% CI: 0.16-0.52, P < 0.001). Consistently, Observational results indicated that TA-PA, which is closely linked to usual walking pace, was independently associated with a reduced risk of sepsis during ICU stay (OR:0.76, 95%CI:0.67-0.95, P =0.026). CONCLUSIONS: Our study suggested that a potential genetic causal link between usual walking pace and reduced sepsis risk, and supported that lower TA-PA was more susceptible to sepsis. It may offer new insights to facilitate the early identification and risk stratification of sepsis.