Grant: Project Grant

Purpose: Blood in the urine, called hematuria, which can be a sign of kidney disease, has generally been neglected in scientific studies despite being associated with kidney failure. The prevalence of hematuria varies widely (0.8% to 31.4%) likely due to differences in measurement and study design. Procedures: Hematuria is caused by a complex interplay of numerous factors, including at the level of DNA, gene expression, proteins, and small molecules (metabolites). In our previous work, we used in-patient diagnostic codes from a large population-based cohort, the UK Biobank, to identify six DNA regions strongly associated with hematuria. We hypothesize that assessing multiple levels of available biological data will provide insight on novel disease mechanisms and pathways involved in hematuria. We will combine hematuria data from the UK Biobank with several other population- and hospital-based cohorts to obtain >120000 affected individuals. Our research team has combined clinical and genomics expertise that has led to an already productive track-record together. Here we propose to extend our work assessing DNA regions by testing whether other sources of biological information (e.g. gene expression, proteins, metabolites) are statistically associated with hematuria. Since association does not necessarily mean causation, we will then employ a robust approach using genetic information to test for causal links with hematuria. This added knowledge will be critical to translate science into clinical practice to maintain and promote kidney health. Outcomes and relevance to patients: We will identify DNA regions and other sources of biological data associated with hematuria in large datasets, and test for causal relationships. Our approach holds the promise of accelerating fundamental discovery that can be translated to targeted therapy for kidney disease.