Robert Plomin - Tracing twins

Kat - In last month's podcast we heard how Professor Robert Plomin and his team at Kings College London have been tracking thousands of twins over fifteen years, recently seeing them through their GCSEs and investigating the genetic components that are linked to academic success. I asked him to explain more about why twins are so interesting to geneticists, and what they can tell us.

Robert - Almost all countries now, something like a hundred countries, have National Twin Registries. The reason for that is the twin method, even in this day of DNA is still very valuable as an initial screen for whether or not traits are influenced by genetics, by heritable differences between people - which fundamentally means DNA differences between them. About 1 per cent of all births are twins, live births, and about a third of those are identical twins are called monozygotic which means a single zygote. A single fertilised egg that in the first couple of weeks of life separates into two clones and they really are clones. They have identical DNA material. In contrast, the other two thirds of twins are called di-zygotic, two zygotes, meaning, two separately fertilised eggs like all first degree relatives, they share 50 per cent of their genes. They're just siblings. So, you can use this then as a natural experiment. If something is heritable that is influenced by genetics, you'd have to predict that these pairs of clones would be more similar because they share 100 per cent of their genes than fraternal twins or di-zygotic twins who share only 50 per cent.

And so, the twin method allows us to look at the extent to which these differences - say in musical ability, which actually hasn't been studied, it's only recently there's been a study done on it - people know it's heritable, the Bach's, the famous Mozart family, that sort of things, but that doesn't prove if that could be nature or nurture. So, the twin method is a good way of screening for genetic influence. And so, when I came to the UK from the US, I was interested in the fact that in the UK, there are national statistics whereas in the US, everything is decentralised to states. So, I wanted to get a national registry of twins because epidemiologically, that just makes a lot more sense to more representative sample of that sort of thing. So, we were able to do that and that created the twins early development study which is a study of all twins born in 1994, 1995 and 1996. So, those twins are now taking A levels and going to university. What we've been publishing on recently is GCSE scores.

Kat - How many twins have you got in this study? How do you track them down and recruit them into this kind of study?

Robert - Well, if 1 per cent of births are twins, you'd expect that back when we were doing it in 1994, 1995, 1996, about 1 per cent of all births is about 7,000, 8,000 pairs of twins born a year. And so, when we studied these three birth year cohorts, we were able to initially identify through both records over 18,000 twin pairs. Amazingly, over 16,000 are the parents of these young twins. This is in the first year of life were interested in being part of the study. Twins are great because parents of twins know their twins are special. You're not studying them because they've got some disease or something like that. They're just normal but their twins and fascinating.

We have a solid bunch of about 7,500 pairs. That's 15,000 individuals who have been participating regularly. For GCSEs, we have that many pairs of twins, and for A levels now. As they go into a university, we've just been funded now. The MRC I should say has funded this all along and we're in our fifth renewal of our programme grant. So, we're now funded to study them through 25 years of age. These cohort studies are very valuable because we carried them through GCSEs but then having 16 years of data on these children from infancy, we've studied them about 12 times over that period. It adds so much value than to add another assessment.

What our pitch now is to say, hardly anyone has studied the transition into what we call emerging adulthood. It's a bit of a buzz word, but this era, it used to be that you went from school to marriage, a job for life, end of story - some people would say. Now, there's this long, long period. It's not like delayed adolescence or something. It's different. There's independence but a sense of trying a lot of things out and on average, it goes on for 8 years, 10 years. And so, it's really a great chance to take these 20 years of data that we have and then use this twin method to study what we're calling sort of functional adjustment to adulthood. We're not going to just study academic skills anymore, but more like the communication skills, the adjustment you need to get through this really wild emerging period of adulthood that we now have.

Kat - In terms of their genetics and their DNA, what are you analysing in their DNA? Are you doing all their genomes? What are you looking at at the DNA level?

Robert - Well we, like everyone else have collected DNA from about 12,000 of these individuals. And so, like everyone else, we're also trying to find genes using the same methods that people use. In general, people realise you need even larger samples. So, there's a big tendency towards collaboration and consortia where you put the data together to get hundreds of thousands of individuals to detect the tiny effects. You need very big samples. So, we're doing that, but what I'm particularly interested in is this tendency towards what we call polygenic scores. So, you don't just take the one or two bits of DNA that look like they're associated with the trait. Say like mathematical ability or achievement in STEM subjects.

Kat - You find like this DNA variation seems to be more common in people who are really good at maths.

Robert - Yeah, that's what an association is. But instead of looking for the 1, 2, 10 or 100, what we're doing is taking tens of thousands of these single nucleotide polymorphisms called SNPs, just DNA differences that are in two forms. That seems to be paying off in a lot of areas of complex traits in medicine as well as in the behavioural sciences. So, once you can do that, you can begin to predict even if you're only explaining a few per cent of the variation in these complex traits. And so, that we can do with our sample sizes and so, that's where we're kind of aiming now.

Kat - So, it's not about pinning down a specific gene or a specific kind of region of the DNA. It's more about the genetic landscape I guess, kind of the whole picture, the tone of the whole picture in someone's genome.

Robert - Yes. It's not every single bit of DNA. I mean, for some traits, you'll find that some 10,000 SNPs are making more of a difference than for other traits. So, it's not the same genes that affect everything. But in the cognitive realm, what's interesting is how general the effects are. I think that's beginning to get the attention of neuroscientists because for a long time, neuroscience was kind of modular. They were looking for which bit of the brain does this and which bit of the brain does that. Other people are saying, "Why are you doing that?" because surely, the brain evolved to be a general problem solver. Instead of making it easy for neuroscientists by finding single tracks between genes, brain, and behaviour, it makes much more sense to take advantage of the little differences that are there in a lot of different systems. So, I think systems approaches, network approaches is what it's about. In genetics, we see that too. People are doing network sort of analyses, whole gene analyses rather than looking SNP by SNP (single nucleotide polymorphism) at a time.

Kat - Robert Plomin from Kings College London.