Protein-based genomic analysis for the identification of risk loci associated with acute respiratory distress syndrome

BackgroundAcute respiratory distress syndrome (ARDS) is a life-threatening lung condition that requires admission to an intensive care unit (ICU). Sepsis is one of the leading causes of ARDS and understanding protein regulation during sepsis could reveal key mechanisms that predispose patients to ARDS. We performed genome-wide association studies (GWAS) on ARDS biomarkers levels to identify protein quantitative trait loci (pQTLs) and genes which could be associated with ARDS risk. MethodsGWAS were performed in 209 patients with sepsis from the GEN-SEP cohort to determine the association of imputed genotypes with 10 serum biomarker levels relevant to ARDS. Measurements were obtained by ELISA within the first 24 hours (T1), 48-72 hours (T2), and 7 days (T7) after the diagnosis of sepsis. We conducted a multi-trait analysis to aggregate the GWAS results for each biomarker at three time points. We prioritized genes in the significant loci (p View larger version (57K): org.highwire.dtl.DTLVardef@1654886org.highwire.dtl.DTLVardef@7c8865org.highwire.dtl.DTLVardef@1dea651org.highwire.dtl.DTLVardef@791901_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG