Genome-wide association study of paediatric bacteraemia and sepsis

Sepsis is defined as a dysregulated host response to infection leading to organ dysfunction. It represents a major global health concern, particularly in childhood. The underlying pathophysiological and genetic mechanisms remain insufficiently understood.

Using samples and clinical data from 650 children enrolled in the Swiss Pediatric Sepsis Study, a national multicentre cohort for culture-proven bacterial sepsis, we conducted within-cohort analyses and a separate case-control analysis in 510 cases and 994 controls, testing genome-wide polymorphisms for association with sepsis susceptibility and, in cases only, with disease characteristics.

In the within-cohort analysis, no significant genome-wide associations were found when assessing host, microbiological, and outcome features. In the case-control analysis, we identified one locus significantly associated with sepsis susceptibility, encompassing the CTNNAL1 and ELP1 genes.

Our results suggest contribution of genetic modulators to susceptibility for sepsis in children.

The Swiss Pediatric Sepsis Study received funding from the Swiss National Science Foundation (342730_153158/1 and 320030_201060/1), the Swiss Society of Intensive Care, the Bangerter Foundation, the Vinetum and Borer Foundation, the Foundation for the Health of Children and Adolescents, and the Sanofi-Aventis Suisse. LJS was supported by the NOMIS and the Thomas and Doris Ammann Foundation.