Peter Donnelly: Human Genetics

Q: What are you trying to achieve in your research?

PD: My research tries to understand the genetic basis of common human diseases. We know that for many or most diseases, like arthritis, and schizophrenia, and diabetes, part of the story that makes some people more likely to develop those diseases (and some less likely), is to do with the DNA they inherit from their parents. That's part of the story. We know that part of the story is also lifestyle, environment, and diet and so on. My research is focussed on trying to learn, for a particular disease, which letters in our DNA, which parts of our DNA code are responsible for some people being more likely to get schizophrenia, which other parts are responsible for someone being more likely to get heart disease, and another person arthritis.

Q: What is the impact of knowing about the genetic basis of these diseases?

PD: There are two different sorts of impact. In some cases, if we find genetic variants which have big effects - and that's true for more rare diseases - then we can use them to identify people who are at high risk of those diseases. At the moment for common diseases, we're not very well placed to do that prediction, but on the other hand, knowing about the genetic variants can give us really important clues into the biology of the diseases. For most of the common diseases, we don't quite know what's causing them or triggering them, and if we can find changes in our DNA which are associated with the disease - if someone having a T in their code at this position is more likely to get heart disease than someone who has an A in that position, in their genetic code - then we can try and work out what the T does, and in contrast what the A does. That will potentially give us a clue about some biological aspect of the disease, what's happening within people to trigger the disease, and in turn we can try and use that information to understand the disease better and to develop new treatments, or new therapies.

Q: How do you carry out your studies and what are your challenges?

PD: Our studies involve collecting DNA from patients with the disease - who are happy to participate in the studies and have consented to do that - and comparing that with the DNA from healthy people. We will typically measure their DNA at a large number of positions, maybe half a million or a million, or possibly even read the entire DNA sequence, all three billion positions in the DNA sequence. We do that in a number of sick people, typically several thousand of them, and compare that with a number of healthy people. Then we're looking at the patterns, or we're looking for patterns which are more similar amongst the sick people than the healthy people, or the letters in the DNA code in particular positions, which are more common in the sick people than the healthy people. Part of my work is statistical, so it's developing methods to try and tease information out of these very large data sets.

Q: What are the most important lines of research that have developed in this field over the past 5 or 10 years?

PD: It's been a really exciting time - there's been an explosion in our understanding and knowledge of the genetic basis of common diseases. If we'd had this discussion six or seven years ago, across all of the common diseases that we suffer from, we knew maybe a handful of examples of genetic variants, which are common and affected people's risk of disease. While five or six years ago we knew five to ten examples, there are now over two thousand examples of documented genetic variants, which affect people's risk of diseases. It's been an extraordinarily exciting time in our ability to learn and understand more about the genetics of common diseases, and that shows no signs of slackening – there's more and more discovery on-going.

Q: Why does your line of research matter, why should we put money into it?

PD: I think studying the genetics of diseases gives us a particular way of understanding the disease. For most of the common diseases, in spite of (in many cases) decades of research, and in some cases hundreds of years of research, we know depressingly little about the key aspects of the disease: what's triggering it within people, what are the differences that cause some people to develop the disease and others not to, or in some cases people who develop a disease to progress well or not so well. Genetics gives us a whole new way of understanding that biology - it gives us new foot-holes into the biology of the diseases. Through understanding the genetics and learning what those genetic differences are doing, we have the chance to understand differences about the disease process. We can then use that information to develop new drugs, to find new drug targets and develop new ways of treating people.

Q: How does your research fit into Translational Medicine within the Department?

PD: I think genetics is a key part, and has a key role to play, in translation. Much of the research is at the basic science end, in terms of the fundamental underlying discoveries, but then it's really important for all of us (and certainly for my own work) to try and work out how we can move that in to the clinic - how we can make differences in medical treatment for people. I think genetics will have a huge effect in clinical medicine over the next ten or twenty years and we're already starting to see some changes. We're starting to see areas where knowledge of genetics - of the DNA variants that people carry, or even of their entire DNA sequences, in some cases knowledge of the genetics of the bacteria of the viruses that make it sick - can already be used by doctors to work out how to adapt treatments or give different treatments. I think genetics is starting to play an important role in translation, and over the next ten or twenty years it'll have a major impact on clinical medicine.