How large DNA banks help us to make breakthroughs possible
By Fiona Calvert | Tuesday 23 February 2021
We know that in the majority of cases, the diseases that cause dementia are not the result of a single faulty gene passed down from our parents. Instead, it appears that small changes in several genes can contribute to disease development. These small genetic changes can affect a variety of different areas of our brain.
Even though risk is a complex mixture of genetics, lifestyle factors and our age, researching genetic risk factors provides scientists with vital clues to understand the biology behind the diseases. They are also the first step towards finding areas which may be useful targets for the development of new treatments.
But how do researchers find genetic risk factors?
The best way to understand genetic changes linked to diseases like Alzheimer’s is through large-scale studies. These studies are known as Genome-Wide Association Studies (GWAS) and at best, involve tens of thousands of DNA samples. The samples are donated by people with Alzheimer’s disease as well as those of a similar age and background but who don’t have the disease.
Researchers can then analyse the genetic makeup of the volunteers in precise detail. They use statistical analysis to look at each gene in our DNA code. The building blocks of a specific gene can vary between people and researchers are looking for variations in the same gene that occur more often in people with the disease than those without it. This flags up genes (the ones we call risk genes) that may be linked to an increased risk of developing a disease that causes dementia.
The bigger the better
The most important thing to remember about these genetic studies is “the more samples the better”.
Investigating Alzheimer’s disease genetics is especially complicated because, due to the multiple factors thought to contribute to disease development, having a risk gene does not necessarily mean you will get the disease. Changes in these risk genes can also be very subtle and therefore hard to detect.
For example, imagine you were investigating a gene. We know that for many genes there are slightly different variations of the same gene that occur naturally in the population. Let’s say for our gene of interest there are two – GENE1 and GENE2.
You suspect that having GENE2 may be a risk factor for Alzheimer’s disease. But because GENE2 is rare, or the effects are small, if you only look in a small number of people – you won’t be able to spot the affect!
However, if you did a larger study with many more samples, you may start to see differences. If you have a large enough set of samples, it may become clear that GENE2 does associate with the disease. These large-scale studies are especially useful for finding genetic changes which are rare or only contribute to Alzheimer’s in certain groups of people.
As researchers find more and more “risk genes” they can also start to look at how different combinations of these genes may work together to increase our risk of developing the diseases that cause dementia.
Genetics and environment
These large-scale genetic studies also allow scientists to tease apart genetic and environmental risk factors. For instance, it might be that all the samples from people with Alzheimer’s disease come from the same area. That means you cannot rule out that an environmental effect contributing to the disease. However, if your sample are from all over the world and from people with very different lifestyles, these environmental effects get diluted out. This makes the genetic effects clearer!
Gathering, maintenance and organisation of genetic data which are large enough to do these studies requires a monumental amount of management.
GWAS studies, along with other large-scale techniques, have already contributed greatly to our understanding of the genetics behind Alzheimer’s, but there is more left to be discovered. As well as helping us to understand why the disease develops, finding these genetic contributions to Alzheimer’s will aid researchers in finding new areas which can be used as targets for treatment.
Since 2014, Alzheimer’s Research UK has supported Prof Kevin Morgan at the University of Nottingham, to build and maintain a huge collection of DNA samples – known as the Alzheimer’s Research UK DNA Bank. DNA banks are an essential tool for dementia research, as often the samples and data are available for scientists all over the world to use. The bank run by Prof Morgan has already helped to identify over 20 new Alzheimer’s risk genes, with more discoveries to come!
This is why Alzheimer’s Research UK encourages and funds the maintenance of large DNA banks such as the one managed by Prof Morgan and his team. The more data available, and the more varied it is, the better chance we have of understanding the genetics of the diseases that cause dementia and translating that understanding into benefits for people with dementia.