Association study of rare variants in human Sepsis

Sepsis is a highly lethal syndrome resulting from abnormal immune and metabolic responses to infection, thereby compromising host homeostasis. Previous genome-wide association studies (GWAS) have identified several genetic loci influencing susceptibility to sepsis disease. However, these loci have shown limited effects and account for only a small portion of the genetic component underlying sepsis susceptibility. In this study, we aimed to uncover rare protein-coding gene (PCG) variants associated with sepsis outcomes. We examined Whole Genome Sequencing (WGS) data of 701 patients with sepsis enrolled in the RHU RECORDS project. After accounting for multiple testing correction, our analysis revealed no detectable effect sizes at our current sample size. Nonetheless, we revealed a cluster of variants situated within the genes TEXT13B, FAM83A, NEDT19, and SLC9A3R1, collectively exhibiting a significant association with sepsis mortality. This knowledge is expected to provide novel insights into potential drug targets for sepsis, risk stratification, and therapeutic response. Characterizing genetic variants associated with sepsis outcomes is crucial to identifying high-risk patients who may benefit from more personalized interventions and individually targeted therapies.

Sepsis is a highly lethal syndrome resulting from abnormal immune and metabolic responses to infection, thereby compromising host homeostasis. Previous genome-wide association studies (GWAS) have identified several genetic loci influencing susceptibility to sepsis disease. However, these loci have shown limited effects and account for only a small portion of the genetic component underlying sepsis susceptibility. In this study, we aimed to uncover rare protein-coding gene (PCG) variants associated with sepsis outcomes. We examined Whole Genome Sequencing (WGS) data of 701 patients with sepsis enrolled in the RHU RECORDS project. After accounting for multiple testing corrections, our analysis revealed no detectable effect sizes at our current sample size. Nonetheless, we revealed a cluster of variants situated within the genes TEXT13B, FAM83A, NEDT19, and SLC9A3R1, collectively exhibiting a significant association with sepsis mortality. This knowledge is expected to provide novel insights into potential drug targets for sepsis, risk stratification, and therapeutic response. Characterizing genetic variants associated with sepsis outcomes is crucial to identifying high-risk patients who may benefit from more personalized interventions and individually targeted therapies.