Amyotrophic lateral sclerosis (ALS, or motor neuron disease), and frontotemporal dementia (FTD) are fatal diseases affecting the brain and nervous system that are increasingly recognised to be related. In 10% of people with ALS or FTD, a single genetic change is identified to be responsible. However, not everyone who inherits such a genetic change will develop ALS or FTD. Therefore, additional factors, including other genes, must be at play. Understanding how different genetic changes interact to determine who will develop disease and what form it takes is vital to preventing ALS and FTD. It would allow us to provide individuals with accurate information about their own risk, identify those at highest risk and work towards ways to reduce that risk.

Using data from 500,000 UK participants, I have shown that a common change in another gene, UNC13A (present in 1 in 8 people), roughly doubles the risk of ALS or FTD in carriers of the C9ORF72 risk gene. My aims are to:

1. Study how other common and rare genetic changes combine to affect risk of ALS and FTD in large population studies
2. Use this information to build genetic risk scores to estimate an individual’s risk of ALS or FTD based on their own specific genetic makeup.
3. Investigate the influence of these genetic factors on what type of symptoms develop and how quickly disease progresses.

Ultimately, this research aims to predict who is most at risk and pave the way for targeted prevention of ALS and FTD.