GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329993/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencing Otherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329993GEOGSEfalseIRF1 rs2057656 Polymorphism Regulates IRF1-AS1 Transcription and Immune Dysfunction in ARDS via Allele-Specific Epigenetic Repression [ChIP-seq]Acute respiratory distress syndrome (ARDS) is a severe and life-threatening variant of respiratory failure. Effective targeted therapies are lacking, and patient heterogeneity is substantial. Interferon regulatory factor 1, a key inflammatory transcription factor implicated in ARDS pathogenesis, has poorly defined genetic regulation. By integrating clinical cohorts with genome-wide association studies, we identified a functional single-nucleotide polymorphism, rs2057656, in the antisense promoter of IRF1. The C allele significantly increased ARDS risk (odds ratio = 3.39). This variant modulates local DNA methylation, thereby regulating the expression of the antisense transcript IRF1-AS1, mediating histone deacetylation at the IRF1 promoter and establishing an epigenetic cascade, DNA methylation, antisense RNA, and histone modification that controls IRF1 transcription and pulmonary inflammation. Exogenous IRF1-AS1 delivery alleviated ARDS in C-allele mice. Our study systematically elucidates an epigenetic mechanism governing IRF1 expression and ARDS susceptibility, identifying a genotype-informed therapeutic target.2026/05/17GSE329993GSM9714810GSM9714812GSM9714811GSM9714814GSM9714813GSM9714816GSM9714815GSM9714818GSM9714807GSM9714817GSM9714806GSM9714809GSM9714808GSM971481916791329993Homo sapiens