Genetic risk factors in critically ill patients with sepsis

Abstract

Sepsis is a severe systemic inflammatory response to infection and is the leading cause of mortality in adults in Intensive Care Units (ICU). Even today, there is a lack of targeted therapies or effective methods for predicting prognosis or risk of death among these patients. In this doctoral thesis, we have leveraged different genomic approaches to reveal genetic factors involved in the risk or the prognosis of sepsis. In this project we have carried out the first admixture mapping study of sepsis, taking advantage of the particular genomic variation of a recently admixed population, such as that of the Canary Islands, exposing a new locus of interest for sepsis susceptibility. Likewise, we have performed the first genome-wide association study of 28-day sepsis survival, identifying new gene variants related to sepsis mortality, as well as the biological processes associated with the worsening of this pathology. Finally, we have analyzed the abundance of mitochondrial DNA copies in peripheral blood early after ICU admission with 28-day survival in patients with sepsis and revealed it as an early prognostic biomarker of sepsis. All these findings have allowed us to better understand the genetic risk and prognostic factors and to identify novel biomarkers for sepsis.