Putative genetic and epidemiological factors associated with development of hemolytic uremic syndrome among verotoxigenic Escherichia coli notifications in Ireland 2017- 2020: a case-control study

Verotoxigenic E. coli (VTEC) infection can cause potentially fatal hemolytic uremic syndrome (HUS). To further our knowledge on the epidemiological and bacterial genomic factors associated with HUS, we carried out a retrospective case-control study with 108 HUS cases and 416 unmatched controls (non-HUS) selected among VTEC notifications in Ireland (2017-2020). Routinely collected epidemiological data on VTEC notifications were combined with genome-wide association study (GWAS) findings. Logistic regression was used to estimate adjusted odds ratios (aOR). Our findings reaffirmed known risk factors [young age (0-9 years), presence of specific vtx genes/gene combinations (vtx2a; vtx1a + vtx2a; vtx1a + vtx2c)], and additionally suggest that having outbreakassociated infection, residence within the East region of Ireland, and the combined presence of both ygiW and group_5720 or both pfkA and fieF genes are potentially associated with developing HUS. Further research is needed to clarify the functional role of these genes in HUS pathogenesis.