Rosa Cheesman: From Mendelian inheritance to sociogenomics

Dr Rosa Cheesman, image courtesy of Rosa Cheesman

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Rosa Cheesman: From Mendelian inheritance to sociogenomics

The Genetics Society’s 200th birthday party for Mendel wasn’t just a lovely opportunity to catch up with old and new friends, drink fizz and eat a pea-themed birthday cake and delicious dinner in a gorgeous setting (oh, my life is hard), but it was also a chance to hear from some of the leading lights in the world of genetics who’ve been awarded the latest batch of Genetics Society medals. 

Dr Sam Behjati from the Wellcome Sanger Institute gave this year’s Balfour lecture about his research understanding how mutations early on in the embryo affect early development - you can hear my interview with him in episode 20 of our last series, Baby Boom.

We heard from Professor Irene Miguel-Aliaga, from the MRC London Institute of Medical Sciences, winner of the Mary Lyon medal, who presented her fascinating research on how sex differences in fruit flies affect their guts and more - and yes, it turns out male and female fruit flies have distinctive poop!

We were then treated to a double-header from joint Mendel medal winners Professors Davor Solter and Azim Surani, my former PhD supervisor, who both made significant contributions to the discovery of the phenomenon of genomic imprinting, or epigenetic inheritance, where genes coming from mum and genes coming from dad are treated and expressed differently in the developing foetus. If you’re curious to know more, check out my interview with Professor Ros John - my former colleague from the Surani lab - in that Baby Boom episode I just mentioned, and find out more about the wonderful world of epigenetics in episode 3 of season 15, Pimp My Genome.

Azim gave us a wide-ranging tour of his work and thoughts about epigenetic inheritance and the origin of germ cells, while Davor dug back into his greatest hits, teasing apart intriguing aspects of gene control. 

However, my other interview of the day was with Dr Rosa Cheesman from the University of Oslo. She’s the winner of the Professor Sir Kenneth Mather prize, which is awarded annually to encourage research in the pure and applied aspects of biometric or population genetics to a student showing outstanding merit in this field.

Rosa gave a beautiful talk showing how she and her colleagues are moving far beyond the Mendelian concept of one gene, one trait, using modern genomic methods such as polygenic risk indices to understand complex human traits and behaviours, including how genes interact with education. 

Looking around at the crowd watching Rosa’s talk, I couldn’t help but notice someone who looked extremely like her sitting in the audience - and, as it turns out, that’s why she got interested in genetics in the first place.

Rosa: Well originally I think my interest was sparked because I'm an identical twin, genetically identical, at least. And I was always responding to the questionnaires keenly and it's always just been a topic of discussion everywhere we go, everyone we meet to like, what are the differences between you? What are the similarities? Why do you think that is? 

So even before I started to do any Genetics, I felt like people were expecting me to be an expert on Genetics and have some answer. Originally, that was what I wanted to study. And then got into the field by emailing and asking if they needed someone to help doing research on the twin study that we were participating in.

Kat: It is that thing. We always describe twins as like nature's experiment because you have, you can have twins that are genetically identical, like you and your sister, you can have twins that are brother and sister or sister and sister, but are not identical or brother and brother. And then you have regular siblings and you have completely unrelated people, and they're such a fascinating tool. 

But I'm interested to know in the world where we have huge cohorts of people and we can sequence millions and millions of genomes. Is there still a place for these kinds of twin studies in teasing out these kinds of genetics.

Rosa: Hmm. I think there absolutely is. I'm biased obviously from being part of a twin study, but I think there are two key contributions of twin studies. 

And one is the knowledge that we've built up over decades and decades of evidence from twin studies. And it's not simply studies quantifying nature v nurture, but we know so much about human differences by studying twins, their extended families. We know about gene environment interactions and correlations and assortative mating. Like there's so much that we need to build on and not just forget about. 

And then secondly, we need this kind of twin data, because even when we have all this amazing DNA information, we can't really interpret it unless we understand the family context and twin, and other sibling and family data can really give us that information. 

Kat: I think it was an interesting point you raised in your talk is like, parents also have genomes that affect who they are and how they come out and their behaviours and characteristics, and not all of the genetic influence in the child is directly inherited in the genes that they get when egg meets sperm. But it is quite complicated the more you think about it and expand out. 

Rosa: Yeah, so genes and the parents are really part of the environment that you grow up in. And yeah, that comes back to your last question about the continuing role of twin studies, because we already know this from decades of research, showing that parenting is genetically influenced and the home environment is partially shaped by the parents genes.

And then now with this DNA era, we can start to learn a lot more about that. And that knowledge is really valuable when we're also interpreting our genetic study results that are based on the children. 

Kat: Now the area you are studying is the role of Genetics in education. And this can kinda be a bit controversial, a bit touchy about why do we even need to do this? Why do we even need to be asking questions about whether Genetics have any role in educational ability and things like that? It seems a bit hot potato. 

Rosa: Yeah, it is a hot potato, and I think it's very good that people are open about it and acknowledge that it's a controversial area because we know that there's this very dark and abusive history of eugenics. And actually there's still eugenics movements and scientific racism going on today. So it needs to be clear all the time. What is the point is it actually valuable?

It's clear from twin studies and now from DNA studies as well, that there is a, substantial contribution to cognitive educational differences from Genetics. These influences don't work in a deterministic way. They work in interaction with the environment. 

I do really think doing genetic research on education can give us a more complete understanding of why we're different and it could lead to social good if we can understand how to create schools and social environments that bring out the best in everyone and not just keep going with the unfair systems that we know we already have.

So Genetics can be used for good, not just misused to have a deterministic view of why people are different. 

Kat: One of the most striking pieces of data that you presented was this kind of curve showing that people who have combined genetic variations in their genome, this thing called like a polygenic risk score or polygenic risk index, that puts them at the lower end of intelligence or ability. They benefit much, much more from the kind of school that they're in. 

So there's more of an impact of schooling for people there than people who are kind of, if you wanna say it, genetically gifted in their cognitive area. So that does tell you something about if, you're a smart kid, almost doesn't matter what school you're in. But actually there could be a lot more to help people and, help their outcomes.

Rosa: Yeah. And I think that it's not gonna be useful in the sense of kind of labelling kids according to their genetic makeup, but more in the use of this for research to tell us for whom are schools most important. And which of the schools, where kids who are lower in the distribution of polygenic scores for educational attainment, in which of the schools where those kids still do really well and how can we make the rest of the schools more like those schools.

So yeah, I think that's where I think Genetics is gonna be useful for research that helps us to understand how schools can work better rather than as a way to label kids which could potentially lead to negative stigmatising consequences.

Kat: Now you are very early in your career. It's a very exciting time for you. You've won this Genetics society award today. Is there a big question that's driving you forward as you pursue your research career? What do you want to aim for next? 

Rosa: Ooh, that's a, that's a big question. I think I want to really make more progress in understanding gene environment interactions.

So an example of that is this study showing that genetic effects depend on the school you are in and vice versa. I think that we really need better data to be able to understand how people's genes lead them to different socially and health relevant outcomes. And we can't really understand that unless we're understanding the social structures that people grow up in, the neighborhoods, the wider regions.

I think now we're at a really exciting time where we're getting the data on families, extended families through history, and we can map the genomes back in time and we can just really start to disentangle this complex interplay between genes and environment.