Approved research

Genetic and non-genetic risk factors associated with Clostridium difficile infection and nosocomial diarrhoea

Lay summary

The primary aim of our research is to identify both genetic and non-genetic factors associated with individual susceptibility to Clostridium difficile infection (CDI). Current understanding of biological pathways and the mechanistic basis for both susceptibility and progression of CDI is limited and this has certainly impacted on the triage, management and prognosis of at-risk patients. This project is part of a larger MRC programme grant initiative that aims to understand how host-pathogen interactions and immunogenetic response profiles contribute to disease progression and patient outcomes, with the ultimate goal to develop more effective treatment interventions for CDI. CDI is a major cause of hospital-acquired infections, accounting for significant morbidity and mortality. Our current prospective studies indicate that the median hospital stay of diagnosed CDI patients is at least twice as long as matched in-patient controls. We aim to use the additional cases available via UK Biobank to overcome the power limitations of previous studies and generate mechanistic evidence for CDI susceptibility, disease progression and recurrence. We believe this clearly falls within UK Biobank's general aim of 'improving the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses'. This project will explore genetic variants, demographic information and biological measurements collected by the UK Biobank in relation to: a) CDI and associated colitis cases against a group of matched controls without the infection. b) Potential relationships and overlap with other gastro-intestinal conditions and intestine-related infections as per ICD-10 codes. c) Longitudinal follow-up in UK Biobank will be used to assess associations between genetic and non-genetic risk factors with disease development and subsequent outcomes for a period of 5 years from case presentation. We want to request access to data for all participants from UK Biobank, allowing ascertainment of cases with evidence of CDI associated colitis, as well matched controls (ratio 1:10) based on their medical and hospitalisation history, and other non-genetic factors (including age and sex). On the basis of ICD-10 codes counts, we estimate that ~100 and ~400 individuals would have CDI or other infectious diarrhoea, respectively, as their main diagnosis; whilst an additional ~150 and ~450 individuals, respectively, would have presented as a secondary diagnosis.