Our aim is to use the UK Biobank data set to better understand congenital diseases of the human immune system over the next three years. Primary immunodeficiencies are rare diseases, but the therapeutic consequences of the diagnoses have a major impact on health care systems. Most primary immunodeficiencies manifest in infancy or childhood. However, there are genetic constellations leading to disease manifestation as late as in adolescence or adulthood. Early diagnosis, i.e. before the onset of clinical symptoms, occurrence of severe infections or chronic end-organ damage, is crucial for early intervention and positive outcomes in these patients.
With these considerations in mind, a population genetic approach is very promising. For the first time on this scale, the UK Biobank dataset provides genetic data, health information, medical records and biomarker studies in parallel. This data will allow us to study not only immunological diseases caused by severe gene mutations, but enables us to use our knowledge from these rare, childhood onset diseases to study also a range of other genetic constellations in which hypomorphic, i.e. non-deleterious, gene mutations play a role. These are known to cause late (adolescence and adult) onset of immunological diseases. If patients with genetic risk constellations could be identified at an early stage – ideally before the onset of first disease manifestations – , the burden of disease and subsequent public health impact could be mitigated by timely preventive measures (ranging from regular health check-ups up to pre-emptive stem cell transplantation).
