Approved Research

Understanding the Impact of Common and Rare Genetic Variants on the Penetrance and Pathogenicity of Human Neurological Disorders

Lay summary

Neurodegenerative diseases are commonly associated with aging.  Neurodegenerative diseases like Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease are caused by progressive loss of neural function.  This loss of function leads to serious impairment in cognition and motor function which then poses a major challenge for societies with rapidly aging populations.

Despite tremendous advances in building a better understanding of the root causes of neurodegenerative disease there are still few therapeutic options for patients.  With few therapeutic options a patient's health and quality of life will be severely impacted.  Our goal is to create medicines that can help patients who have serious inherited forms of neurological diseases and are out of options.

To be able to develop novel medicines we first need to understand the nature and consequence of the hereditary defects that underpin neurodegenerative disease. Genetic association studies are a powerful tool that has revealed a remarkable range of discoveries that improve our understanding of the underlying biology of inherited diseases.  These discoveries have revealed new biological pathways involved in disease which greatly contributes to our understanding of the cause and effect of disease-related hereditary defects.  This increased understanding opens new avenues for development of novel medicines for patients.  Access to very large datasets such as the UK Biobank can considerably improve the power of these genetic association studies.

Neurodegenerative diseases are complex disorders because both genetic and environmental factors contribute to the risk of onset and progression of the disease, with each variant having only a subtle effect.  To help us to better understand these effects we will combine what we learn from the UK Biobank data with findings from own research to help us to construct better models of diseases.  These models will be used to identify genetic risk factors that predispose individuals to inherited neurodegenerative diseases. 

Knowledge gained from this work has the potential to contribute directly to the discovery of novel medicines aimed at combating neurodegenerative diseases and dramatically shorten the time for development of treatments that can enter clinical testing.  Without this information such efforts can often take more than 10 years.