biostudies-literatureShen RNational High Level Hospital Clinical Research FundingNational High Level Hospital Clinical Research Funding-Elite Medical Professionals Project of China-Japan Friendship HospitalNational Key Research and Development Program of Chinathe National Natural Science Foundation of China29523https://www.ebi.ac.uk/biostudies/studies/S-EPMC11603036biostudies-literatureUnknown14(1)Acute respiratory distress syndrome (ARDS), with high morbidity and mortality, is a common clinical syndrome of acute respiratory failure caused by diffuse lung inflammation and edema. ARDS can precipitate in various ways. The complex pathophysiology of ARDS involves the activation and dysregulation of multiple metabolisms and immune responses. Using summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of 179 genetically predicted lipid species and ARDS (375 cases, 406,518 controls) was performed and validated in plasma and pulmonary edema fluid from 24 patients. Furthermore, we used a two-step MR to quantify the effect of immune cell-mediated lipids on ARDS. We identified 8 lipids (Cholesterol, Phosphatidylcholine (14:0_16:0), Scientific reportsCausal relationship between lipidome and acute respiratory distress syndrome.PMC1160303682270108National High Level Hospital Clinical Research Funding2022YFC2504401ZRJY2023-GG21Xia JQi ZHuang XZhan QShen RfalseCausal relationship between lipidome and acute respiratory distress syndrome.Acute respiratory distress syndrome (ARDS), with high morbidity and mortality, is a common clinical syndrome of acute respiratory failure caused by diffuse lung inflammation and edema. ARDS can precipitate in various ways. The complex pathophysiology of ARDS involves the activation and dysregulation of multiple metabolisms and immune responses. Using summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of 179 genetically predicted lipid species and ARDS (375 cases, 406,518 controls) was performed and validated in plasma and pulmonary edema fluid from 24 patients. Furthermore, we used a two-step MR to quantify the effect of immune cell-mediated lipids on ARDS. We identified 8 lipids (Cholesterol, Phosphatidylcholine (14:0_16:0), 2024-01-01T00:00:00Z2024 Nov2026-06-01T13:23:32.404Z2025-04-04T22:47:28.999ZS-EPMC116030363960446410.1038/s41598-024-80985-z