Meaghan Jones - Asthma and epigenetics

Kat -  Now it's time to return to our theme of cohort studies. It's not just Bradford - large-scale studies are ongoing all around the world. And it's not just genetics that they're looking at - there's epigenetics too, a topic we covered in the past couple of podcasts. Meaghan Jones, at the University of British Columbia in Vancouver, Canada, is studying a group of Canadian children, known as the CHILD study - looking at the genetics, epigenetic and environmental triggers of asthma and allergies, from the very earliest stages of life.

Meaghan - Things that happen to you in utero during pregnancy when you're in your mother's womb or early in life lead to health outcomes later on. There are a lot of examples of these. We know about these things already. We know things like children who grew up in adverse environments, if they grew up in a poor neighbourhood, lots of violence and crime in the neighbourhood, they have worse health outcomes, especially things like cardiovascular disease, later in life. So, we know the connections exist, but no one knows why. And so, we're trying to find out if we can find molecular mechanisms that explain some of those connections - how do we see what's happening physically and on a cellular level to connect a prenatal exposure with later health outcome.

Kat - How definite are these links because it sounds kind of scary thinking, oh my goodness, something that your mother did when she was pregnant with you and maybe when she didn't even realise she was pregnant with you could be dooming your forever into a life of ill health?

Meaghan - Yeah, that's a really good point. It is not all doom and gloom in this field at all. It's definitely not deterministic. The kind of things we work on are very plastic. They're very changeable, but they are sometimes indicators and they're indicators of risk. So, like I said, the example about children growing up in poor neighbourhoods and heart disease, it's not that every child that grows up poor is going to grow up to have heart disease but they are at increased risk. So the nice thing is if we can start teasing out some of the mechanisms figuring out why this has happened, we can figure out the kinds of interventions that can prevent the health outcome in the future.

Kat - What kind of diseases are we talking about? You've mentioned heart disease, but what other sort of things might be linked to these kind of early exposures?

Meaghan - So, one of my major studies is on asthma and allergies. Development of the immune system is very sensitive to insults and we know especially in the western world that incidence of asthma and allergies is growing by leaps and bounds. We don't know why. There's the idea of the hygiene hypothesis - in the western world, we're not exposed to the natural environment the way we used to be.

Kat - Not enough filth basically.

Meaghan - Yeah, we're too clean. We don't go hanging around with cows and chickens in the yard, and that makes your immune system start to overreact if it's exposed to things that are not actually dangerous like pollen or cat hair, or any of the other things that there's no reason for your immune system to act like that way.

Kat - So, how do you start looking at these kinds of links between these early exposures and later effects on the immune system?

Meaghan - So, we will take advantage of what's called natural experiments, which is a fancy term for cohort studies - some amazing kind people who are willing to sacrifice time and effort to be parts of our studies. I work on one of this big Canadian study- it's called a Child Study - big cohorts within Canada. All they did was put up posters in waiting rooms of prenatal clinics and said, "Would you like to be part of a study?" 3500 women in Canada signed up and they're still there 3 years down the road. They come in once a year, they're collecting data, they fill the questionnaires. So, these natural experiments take advantage of the variability exists in the population. We just ask everyone. Anyone who's interested can come in and that gives us a really nice cross-section of the kinds of things that actually exist.

Kat - What sort of things are you looking at then to try and work out, might have an influence later on? What sort of things are you measuring?

Meaghan - We're measuring something called DNA methylation. DNA methylation is a mark on your DNA. It doesn't change the sequence of your DNA at all, but it adds a little bit of a chemical group at specific sites in the genome. The only thing that that does is it affects the way that your genes are turned on and off. So, we think because it's not changing the sequence, because it's very changeable, it can be put on and taken off sort of at will, that it's more responsive to the environment. But it may stick around after its usefulness, is the idea. So, if you're exposed to stress, if your mum is having a stressful time during her pregnancy then your immune system may start reacting to stress because biologically, physically, you're reacting together with your mum. But after you're born, you don't necessarily need to keep that same active mark on and it might stick around afterwards.

Kat - Where do you think we are with being able to definitely link some of these epigenetic effects to actual health outcomes in the long term?

Meaghan - Yeah. We're not there yet. Right now, it is very correlational. So, what we do is we take large groups of people, the bigger the better, and we say, "Do we see patterns in these people that are different from another group of people?" So, that's just correlative. We can't say anything about causation yet. The thing that's really exciting about the field is this is all brand new. We don't actually have that much even at this preliminary stage yet. So, we're still building on that and that's why it's really exciting to be working in the field.

But the next stage is - we're starting to get there - which is validation. That's the first thing you need to do. Once you find something in a group of people, you have to find another independent group of people and find the same thing or it may just be an effect of the specific group you looked at. After that, once we start finding these effects, we need to drill it down a little bit more closer into the molecular mechanisms to find out whether the patterns that we're seeing are actually having an effect. It's going to be a long road, but if it was easy, anyone could do it.

Kat - That was Meaghan Jones from the University of British Columbia.