Abstract
BACKGROUND: While previous observational studies have suggested a link between frailty and acute respiratory distress syndrome (ARDS), the causality of this connection remains unclear. The objective of this study was to explore the potential bidirectional causal links between frailty and ARDS. METHODS: A two-sample univariable Mendelian randomization (MR) was performed to assess the causal relationship between frailty, as defined by frailty index (FI, n = 175,226) and fried frailty score (FFS, n = 386,565), and ARDS. The genome-wide association study (GWAS) data of frailty was from the UK Biobank and the ARDS data was from the FinnGen Database. Univariable MR analyses were conducted using inverse-variance weighted (IVW), weighted median, MR-Egger regression, and robust adjusted profile score (MR. RAPS). We also performed multivariable Mendelian randomization (MVMR) analysis including smoking initiation, alcohol consumption, body mass index (BMI), and cognitive performance. RESULTS: This bidirectional MR analysis demonstrated no causal effect of FI (OR = 0.96, 95% CI 0.14-6.88) and FFS (OR = 1.95, 95%CI 0.14-28.16) on increased susceptibility of ARDS. Also, no evidence was found for an effect of ARDS on the risk of frailty. The MVMR analysis indicated higher BMI and poorer cognitive performance were associated with increased risk of ARDS. CONCLUSIONS: The outcomes of our analysis imply a probable absence of a direct causal relationship between frailty and susceptibility to ARDS. To reinforce and expand upon these preliminary findings, it is imperative to conduct larger-scale genome-wide association studies.