[Aims and Scientific rationale]
Although many diseases can directly be linked to genetics, the outcome for a given individual is not predictable and depends on many factors, many unknown. The aim of this proposal is to use health and genetic information to divide the patients into subgroups to help us develop a hypothesis of whether an individual within a subgroup is likely to develop the disease and whether our therapeutic strategy is likely to help ameliorate the disease condition. The large number of samples and thorough clinical evaluations within the UK Biobank enables associations to be observed many times, reinforcing confidence in genetic findings – smaller biobanks are often insufficient for such studies.
[Project Duration]
The proposed studies are overlapping, each comprising a set of question and analyses that take 3-6 months to develop. Reports will be produced at regular intervals.
[Public health impact]
This work will impact indications with significant unmet needs including monogenic disorders, such as Friedreich’s Ataxia that leads to cardiomyopathy and neurodegeneration over time, and common diseases with genetic risk factors, such as glaucomatous optic neuropathy. Our expectation is that the proposed studies will (1) provide the genetic evidence for initiating studies on new therapies; (2) will provide novel genetics understanding that can be used to choose a population most likely to benefit, or conversely should not take a certain drug; and finally (3) will provide new readouts for drug effect.