We propose to harness the power of large-scale genomic analysis to understand the interactions between human genetic variants, persistent infections, chronic inflammation and complex human diseases of major public health importance.
Combing data collected in the context of the UK Biobank cohort and the Swiss CoLaus cohort, this study aims to identify the major genomic determinants of humoral immune responses against multiple persistent human pathogens. A GWAS strategy will also be used to describe the influence of human genetic factors on the plasma levels of inflammatory biomarkers (e.g. CRP), which are correlated with certain persistent infections. Genetic risk scores will be built to summarize the combined effect of associated variants on infectious and inflammatory phenotypes. Finally, we will develop statistical models to explore the respective and combined influences of genetic variation, persistent infections and low-grade inflammation on complex human diseases (coronary artery disease and neurodegenerative disorders). These analyses have the potential to elucidate important pathogenic mechanisms. From a translational perspective, outcomes of this project could thus include novel disease biomarkers, better prediction models, or innovative targets for diagnostic or therapeutic development.
