Genetics of Obesity and Diabetes
Epidemiologist Nick Wareham on leptin, type 2 diabetes, and genome-wide association studies
The video is a part of the project British Scientists produced in collaboration between Serious Science and the British Council.
Twin studies are an amazing asset to science, they are a unique natural experiment. Something you can do in humans that you can’t do outside laboratory animals, it is the equivalent of a cross-mating experiments in animals. Basically, there are two types of twin: identical twins who share all their genes and non-identical twins who share only 50% of their genes. Both types of twin share their environments to the same degree. So if you want to find out if any trait or any disease is dominated by nature or nurture, by genetics or environment. You compare the similarities of these two groups of twins. And if you see a greater similarity in the identical twins, compared to the non-identical twins you know that that trait has to have a genetic component. And then you do some simple maths which gives you a difference between the correlations and you get what is called the heritability, which is another way of saying the proportion of any condition that’s due influenced by genes.
On average, for most of the human traits we look at, we tend to see around 60% of the differences between people explained by their genes. And twin studies are pretty much the only way you can get at this figure, the only way you can separate nature and nurture. Because if you just looked within a family, at, say, a mother and a daughter, you might see some similarities, say that they were both on the large side or very short in stature. But you wouldn’t know that’s because they shared the same social conditions, the same food habits, malnutrition or overnutrition. So it’s only by having these two sets of twins that are otherwise identical in every way except for the sharing of the genes that you can make these clear distinctions between the two.
And over the last 25 years since I set up the Department of Twin research, here at King’s College London, we’ve made a large number of discoveries in many of the common diseases. Many diseases that people thought before were just either due to chance or due to age, just a simple wearing out of the body. And some examples are cataracts of the eye, when the eye fogs over, we know now that that has a strong genetic component. Osteoarthritis is common in about one in three people. And most people know somebody or one of their parents is having it, and that has a strong genetic component, as does back pain, which people thought: «all that should be impossible, the back pain that’s just a mechanical problem». But no it’s three times more genetically influenced than something like breast cancer.
So our studies, along with other twin studies around the world, and there are perhaps six or seven large groups around the world that we often collaborate with, have made a very large contribution to understanding common diseases related to aging, but also related to some other traits that people perhaps didn’t think at all were genetic. Something like your preference for food: whether you prefer spicy foods or you like garlic. I personally thought that would be environmental, but it turns out actually it’s quite strongly genetic. Whether you like Korean spicy kimchi or broccoli, or you don’t like it. Often these are strong tastes, turns out that our genes are behind them. Then that also means that whether you like salads, or you like fish and chips, unhealthy foods, junk foods, also have the genetic basis. So that was interesting. Personality is another trait that has been known for many years and in general whether you are an optimist, or an introvert, or an extrovert, whether you are very conscientious, anxious, neurotic, – about 50% of that comes from your genes and about 50% comes from your environment. Things like cigarette addiction, alcohol addiction, how much you drink is strongly heritable, strongly genetic.
And then we have some other interesting traits, because we tested our twins here at King’s College just before the last general election. When David Cameron was running for prime minister and we asked the twins how they would vote. It turned out that voting Conservative or voting Labor, so left-wing or right-wing, was 60% genetic. And so even something that we think is our free will turns out to have an influence of our genes. The one fact surprises most people about twin studies and something that we’ve also looked at was belief in God. Now, religion, known as the opium of the masses by some, is obviously a very important aspect of people’s culture around the world. But it turns out that whereas your religious affiliation or whether you go to church, or your mosque, regularly is not genetic, that’s a cultural trait. What is genetic is how strongly you believe in God and how spiritual you are. And studies the we’ve done also in Finland, the Netherlands, Australia, and America show the same thing – the rate of a 50% heritability of belief in God.
Now, what these studies all mean is that there is the starting point for the research in how you can actually find the genes underlying it. And so we can start by using genetic testing, using a million markers across many twins or unrelated individuals, comparing these genetic markers with these traits whether it’s back pain, whether it’s breast cancer, or whether it’s belief in God. You can find the underlying genetic variants that explain these traits. That’s what we’ve been doing for the last eight or nine years. We’ve discovered at least 500 genes in at least a hundred traits and diseases. Nearly all these studies are done as global collaborative studies with colleagues all over the world. Some studies as big as half a million people. We’ve just finished a study recently looking at hair color. We took data from the British Biobank combined it with some data from 23andMe, which is an American company that does population screening, people pay for having a test, looked at hair color. It turns out we have hundreds of different genes that control our hair color. Whereas we thought there were just a dozen before that.
Twin studies are a very nice way of starting off a new area of research moving people to realize that nearly everything that distinguishes humans from each other has some genetic basis, meaning that we can understand the genes behind them. That’s why they’re particularly exciting.
Now, the other way of using twins. I told you about how you compare one with another, but if you take just the identical twins, the genetic clones, they’re also fascinating, because any difference between them can’t be due to genetics it must be due to environment. We’ve also looked in this way at twins reared apart, twins where one is higher up on the social scale than the other, we’ve looked at signs of stress, for example. That’s the effect of being a socially distinguished country where you have different social classes and the effects on health. Whether one is married or unmarried, things are very hard to otherwise distinguish, where one is overweight and the other is skinny, or one is religious and non-religious, to look at those differences. So that’s a really nice model as well where you can use twins, which is a bit like doing a lifelong clinical trial, but this way you have a matched clone, who’s gone through life either smoking, or not exercising, or doing something you can compare to.
That’s particularly good. We’ve also been using it for something called epigenetic studies, which is complicated. Epigenetics is the study of how you can just switch on genes, on and off, a bit like a light switch, with these chemical signals. So even identical twins have different epigenetic signals, which explains why even identical twins often die of different diseases and have rather different profiles and personalities.
So in the future twin studies are really going to tell us a lot about ourselves. They’ve already told us how much we vary from each other and why, we explained that. But I think we’re moving away now from genetic determinism, we’ve gone through this in the last 10 years of saying ‘genes are crucially important’. We realized by studying identical twin pairs that the fact is that they often go in different directions with the same genes shows that the genes themselves are not enough. There’s many other factors that are playing on them that determine us. And so we’re much more flexible than we believed. And I think, identical twins particularly are getting very useful for personalized medicine showing us the limits of which we can predict, how someone will behave based uniquely on their DNA and their genetics structure. Because by following these twins over time, we see very different trajectories. And the fact that if you follow them they die of different diseases at different times despite having identical genes tells you the limits of a purely genetics-based prediction. So I think, if they’re going to be really useful for just informing us. It’s actually much more difficult to predict how humans end up than perhaps we’d been led to believe by other scientists.
Epidemiologist Nick Wareham on leptin, type 2 diabetes, and genome-wide association studies
Zoologist and entomologist Sean O'Donnell on Army Ants, chemical weapons, and invasive species
Physicist David Southwood on the history of the Cassini mission, landing on Titan and why does humanity need t...