The risk gene riddle


By Fiona Calvert | Tuesday 02 March 2021

You may have seen us talking about risk genes for the diseases that cause dementia a lot recently! To date scientists have identified over 70 “risk genes” for Alzheimer’s disease and the numbers are always increasing.

But you may also know that risk genes alone can’t predict whether a person will develop dementia. So why do researchers spend so much time looking for new ones?

It turns out that risk genes are a really important piece of the puzzle that helps us build our understanding of how a disease progresses.

Back to basics – our genes

Every cell in our body contains thousands of genes. Each gene is a portion of DNA ‘code’, which holds the information our cells need to make a specific protein. These proteins are the building blocks of life. They make up our tissues and organs, and many have specific functions, like carrying messages between our nerve cells.

Risk vs faulty genes

The biggest thing to remember when thinking about the genetics behind the diseases that cause dementia – is that risk genes are very different to faulty genes.

In very rare cases a person may inherit a gene from their parents that does not work properly and will ultimately cause dementia. This is a faulty gene, sometimes called a gene mutation, and can cause a person to develop a disease no matter what other risk factors they have. This is true for rare types of Alzheimer’s disease and some cases of frontotemporal dementia.

But in most cases our chance of developing dementia is a complicated mix of age, lifestyle factors and genetics. This is where risk genes come in. These are small changes in genes that can increase our likelihood of getting a disease. And having these risk genes doesn’t mean you’ll definitely get dementia!

Risk genes in research

Understanding how genes combine with other risk factors (like our lifestyle or age) to impact someone’s chances of developing a disease is just one way that genetics plays a role in dementia research.

But finding new risk genes also has a huge impact on how researchers develop their understanding of how diseases work.

A list of risk genes for a disease is like putting together the edge pieces of a puzzle – it doesn’t show us the full picture, but it creates a guideline that means filling in the middle is a little bit easier.

If scientists know that a specific gene increases the risk of developing a disease, it means that gene and the protein it makes are probably involved in disease progression in some way. Researchers can then start to look at the processes those genes are involved in and potentially identify new treatment targets.

For instance, in 2012 scientists identified variations in the TREM2 gene that increase a person’s risk of developing Alzheimer’s disease. TREM2 is involved specifically in the immune system in the brain. The identification of this risk gene provided the strongest evidence that the immune system may play a key role in the progression of the disease.

This discovery has led to 22 potential new drugs targeting the immune system in clinical trials.

TREM2 is the perfect example of why finding risk genes is so important. Looking at an individual person’s TREM2 gene won’t be able to predict their chances of developing dementia but the discovery has moved us a stepped closer to finding a life-changing treatment for dementia.

Alzheimer’s Research UK and risk genes

We know that finding new risk genes is a vital part of dementia research. That is why since 2008 we have funded Prof Kevin Morgan to expand and maintain a DNA bank. This large-scale resource alone has helped to identify most of the risk genes we know about.

The samples and data generated through this DNA bank are also open for researchers all around the world to access. This means other scientists can build off Prof Morgan’s work, accelerating progress. The team working at the DNA bank have collaborated internationally to look at the genetics of over 35,000 people with Alzheimer’s disease.

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Fiona Calvert