Approved research

Infer genome-wide cell-type specific regulatory element activity for phenotypes of the UK Biobank

Lay summary

To date, researchers have identified that thousands of genomic locations that can cause and regulate complex traits, such as heart diseases, diabetes and cancer. However, despite the marked advance in knowledge about genetic architectures of complex traits, we still only have few successes in validating these findings in biological experiments. One main challenge for experimental validation is to identify disease relevant cell-types to work with. Many diseases are driven by improper/corrupt function in a particular type of cell. For example, diabetes is associated with pancreatic islet cells and rheumatoid arthritis is associated with a particular type of T cells (CD4+). We therefore argue that identifying the specific disease-driving cell-types is key to improve our understanding of how the disease works so that ultimately, we may cure the disease. In this study, we aim to identify which parts of the DNA are most likely causing big changes on the cell level and consequently driving diseases. We will analyze UK Biobank data using a novel in-house developed method named IMPACT (Inference and Modeling of Phenotype-related ACtive Transcription), in 24 months time. This work will provide key knowledge of disease mechanisms and will expedite drug target research and therapeutic interventions. As such, our goals are aligned with UK Biobank's aim of enabling research to improve 'prevention, diagnosis and treatment of illness and promotion of health throughout society'.