Dalton Conley: People, they never heard of it before. They’re so fascinated by the idea that there’s this score that can predict their outcomes based on their genes.

Paul Rand: You may think of genetics as something that determines your height, your eye color, or maybe even your health risks, but what if I told you that your genes could predict so much more about your future?

Dalton Conley: Genetic prediction has been moving forward at a very fast clip.

Paul Rand: That’s Dalton Conley, a professor of sociology and the author of a new book, The Social Genome, which explores how something called polygenic scores, essentially prediction algorithms based on your genes, are allowing us to estimate with disturbing accuracy things about your life that blur the line between reality and science fiction.

Dalton Conley: Things like how much money you make as an adult or how far you go in school.

Paul Rand: Once you start to dig into the science, it can honestly be a bit shocking. Some studies find that variations in genes can not only predict your future income, but on a societal level, explain 58% of the variations in income in males and 46% in females. That means our genetic differences may explain about half of where we end up on the income ladder.

Dalton Conley: I’m surprised that people are surprised by that because if you think about it, nobody’s that shocked that height has a genetic component or that your immune system maybe has a genetic component or any other attribute that’s about you physically might have a genetic component. But then the moment we get to brains, people all of a sudden think, “Oh, there’s no genetic component.”

Paul Rand: What’s fascinating and a bit alarming isn’t just what our genes tell us about ourselves, but what they reveal about our society.

Dalton Conley: There’s a number of surprises, like how much we’re sorting on our genes in society.

Paul Rand: We’re sorting ourselves into genetic silos. We marry, socialize, and even choose where we live based partly on our genetic predispositions.

Dalton Conley: Unbeknownst to ourselves and what that means for future generations where we’re going to be separating out not just socially but genetically.

Paul Rand: Could this lead us down a path toward deeply entrenched inequality, one that’s literally coded into our DNA?

Dalton Conley: Genetic sorting is going on in society in terms of marriages, in terms of friendships, in terms of literally where we move and live. And now we are having more and more babies being born that have been polygenically selected. So yet we’ve had almost no discussion about talk about AI. We talk about gene editing, but we have not talked about genetic prediction as a revolutionary technology, and I think that conversation is what’s scary to people.

Paul Rand: One way out of this dilemma takes us back to one of science’s most foundational debates. You’ve all heard this, nature versus nurture

Dalton Conley: The idea that for some outcome, cognitive ability or personality type, that is partly determined by just the genes you inherited from your family and partly determined by the environments that you encounter in your life, the random environments. And what I show in the book, The Social Genome, is that the whole question is misguided. So there’s been in the last 50 plus years, thousands of studies of twins, comparing fraternal and identical twins to see, which gives you a way to back out how much is “nature” and how much is “nurture.” And a recent paper meta-analyzed all of those, looked at all the studies, thousands of studies on hundreds, if not thousands, of traits. And the median or average heritability, meaning the nature side across all those traits was 49%, and 51% was environmental.

Paul Rand: We can’t control the genes that we’re born with, but we can shape the environment in which those genes express themselves. Conley’s research reveals something profound. It’s not just nature versus nurture, but how deeply interconnected the two of them are.

Dalton Conley: There’s no nature versus nurture. They’re really integrated. How your genes matter depends on the environment. How the environment matters depends on your genes,

Paul Rand: Change the environment and we may change how our genes impact our lives. Change how they impact our lives and we may be changing society. And getting a grip on what changes we want to make is going to become crucial because these genetic prediction techniques are arriving faster and faster whether we’re ready or not.

Dalton Conley: In terms of the applications of the science, whether or not they’re dubious or not, whether or not they merit getting out into the world, yet I’m sure they are going to get out.

Paul Rand: From the University of Chicago Podcast Network, welcome to Big Brains, where we explore the groundbreaking research and the discoveries that are transforming our world. I’m your host Paul Rand. Join me as we meet the minds behind the breakthroughs on today’s episode, what genomics is telling us about how to shape our society.

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Al, right, and for us to really understand this, the basic concept I think we’ve got to get our arms around is this idea of the polygenic index. Help me understand what that actually is and why it matters to this discussion.

Dalton Conley: Basically, the polygenic index or polygenic score, there’s a lot of names for it. Polygenic risk score, genetic risk score. When we do studies called genome-wide association studies, which we look all across entire 23 pairs of chromosomes and look at these little variants where you might have two thiamines and I have a thiamine and a cytosine, there’s four bases in DNA and you can swap out. So in about one-tenth of 1%, there’s common variation among humans. One out of every thousand bases, you can see differences in the population and that’s I think where you get the term we’re all 99.9%-

Paul Rand: Alike.

Dalton Conley: Alike, yeah, genetically. So when you just see which of these matter, you just see, well, people with CT, are they shorter or taller than people with TT and are they shorter or taller than people with CC at this location? And then you do that three million times across the genome and you get answers. Whether or not you’re tall or short is not a few genes. It’s the sum total of all of these little perturbations across your entire genome. And what a polygenic index does is basically take all of those little teeny effects and sum them into a single number, and that single number, I call it the FICO credit score of human biology, which is that it predicts your height or how far you’ll go in school or how neurotic you are or likely to be depressed.

Paul Rand: Let me pause on this point. The idea that your genetics’ going to determine your height, you’re likely to inherit diseases, your eye color, any number of things people probably pretty much have their minds around. It’s a understood concept. The idea, though, that you could look at genetics and that can actually talk about how well you’ll do in school, if you’re going to end up making a lot of money, this is where some new thinking really starts coming into this. This is the other side of the equation that may have thought more about what nurture could have provided or other ways. Is that getting it right?

Dalton Conley: And think about the fact that even if genes determine whether or not you’re more or less likely to get ill, if you’re unhealthy, you’re not going to go as far in school generally. You’re not going to do as well in the labor market. So there are a whole bunch of mechanisms by which genes affect those kinds of things, like whether we’re wealthy or we’re poor, that have nothing to do with cognitive ability. There’s many pathways. There’s pathways through addictive behavior, for example. There’s pathways through height and beauty that we know that beautiful people are more rewarded in the labor market.

I think when people stop and realize, oh yeah, all those things determine how far people go in the socioeconomic rat race, then they’ll be less shocked that genes matter for those kind of social outcomes, socioeconomic outcomes. So height is between 80 and 90% in our genes in a modern society where there’s not massive famines all of a sudden and other big environmental shocks, but something like how far you go in school is 40% variation in their genes. But for cognitive ability, it’s getting closer to height, like 75%. And for personalities, again on the lower end, like around 20%.

So different traits have different amounts that the genes are driving the show, but the point in my book is that they need the environments in order to realize their effects. To take an example, there’s genetic variation in body mass index and how fat or thin we are, but in the early 20th century, everybody had to work really hard. We had much less sedentary lifestyle and there wasn’t venti frappuccinos with 1,000 calories to choose from versus the cal salad at the local Starbucks. So the effects of the people’s genes were suppressed by the low calorie, high work environment. And now we live in almost unlimited calories or choice of what to eat, and we have a more sedentary lifestyle and those genes now matter. So the BMI polygenic index for body mass index predicts much better now than it did in early the first half of the 20th century.

To take another example, women were largely blocked from higher education in the first half of the 20th century, and only in the last third of the 20th century did women have complete access to higher education, and now they exceed men in terms of the number of bachelor degrees they get. And if you look at polygenic index for education, it did not predict for women very well in those cohorts of women that grew up, let’s say before the 1960s, but it predicts much better now.

So the environmental landscape matters, and that’s because a lot of genes, they’re not akin to architects building specs like you’re going to make this person this tall with this many stories and this many apartments exactly laid out this. Genes are more like an AI algorithm. We’ve got this tool. Go out and find some data in the world. And it seeks out data that the more you’re exposed to the world, to the environment, the more the genes come into focus and matter more. And that’s because we sort into our environments. We evoke different responses. We extract different information from the environment. So the environment is critical to how those genes realize their effects and which means that we’re not also... It’s not some deterministic world the way Galton or Mendel might’ve imagined it 150 years ago, where genes are just on off switches. They’re complicated circuits with the outer world. They don’t stop at your skin.

Paul Rand: Now, you talk about this idea of the genes in the environment in three buckets, which is passive, evocative, and active.

Dalton Conley: Yeah.

Paul Rand: Help explain that in some of the contexts that you’re going down.

Dalton Conley: Well, let me start with active. That was observed by Darwin, as far back as Darwin, that we create niches in the environment based on our genes. I mean, that’s something as simple as I have zero working copies of the fast twitch or sprinter’s gene in my genome personally, so I’m not fast. So I’m going to avoid the track and field. I’m going to probably avoid the soccer field. The kid who has the high polygenic score for cognitive ability or education may veer to a certain activities and the kids who have a high polygenic score for athleticism or for musical ability are going to choose dad, mom, I want to go to music summer camp. They’re going to choose their environments based on their genotype. So evocative is when someone else shapes their environment in response to my genes.

For example, skin tone is largely controlled by genetics. Paper by myself and colleagues that shows that comparing siblings, it’s really random which brother, let’s say, or which sister got darker skin and which kid got lighter skin based on their genes they happened to inherit from their parents. And the kid with the darker skin is much more likely to end up with high blood pressure than the kid with lighter skin. And we show that that’s not because of a direct effect of the skin tone genes on the cardiovascular system. It’s really because darker skin evokes more stress in their lives compared to their lighter skin siblings. We know that people who are taller, which is genetic evoke, are treated differently. People who are beautiful, facially, symmetric and so forth, which is controlled by their genes, they are thought of as smarter. They’re treated nicer.

So anything that evokes a different response in the world, you’re wearing glasses, if people treat you differently because of your myopia, that’s an evoked response of your genes. Passive gene environment connection is when your genes are just non-randomly distributed in the environment because of the active or evocative gene environment connection in past generation. So in other words, if I have gene for depression, let’s say, I inherited those genes from one or both of my parents.

Paul Rand: The other thing that you brought in this idea is that this concept of The Social Genome, and you mentioned this a second ago, but that the DNA of the people around us shape and is part of our environment too. Explain what you mean by that.

Dalton Conley: To me, that’s one of the most exciting parts of this. It’s just a syllogism. The people around you, the important people in your life, your parents, your children, your peers in school when you’re growing up, they matter to how you turn out and their behavior is partly driven by their genes. So we can actually study their genes and study how their genes predict how you turn out.

One example of this that Ramina Sotoudeh from Yale University, my former student and I worked on was peer influence of smoking. So we compared within a high school that this year’s junior class had a certain distribution of smoking polygenic indices as compared to next year’s junior class or last year’s junior class. And we showed that if we’re looking within a high school, the year-to-year variation in the distribution of genetic scores for smoking in a given grade is random. So we’re treating that as a random experiment. One kid is happens to be in the junior class this year, and there’s a handful of kids in that grade who have really high polygenic scores for smoking. And another kid in the same school with the same polygenic index themselves for smoking is in the next year’s junior class. And there are really no... There may be just one student at a very high end of the smoking distribution for the genetic risk for smoking.

And what we found was that those quote “bad apples” with respect to the genetics of smoking can affect an entire grade.

Paul Rand: Amazing. Okay.

Dalton Conley: So the grades that have more kids who are at the extreme and very likely to take up smoking end up creating a contagious effect across the entire social network. And that even if I don’t know those kids personally because I don’t share the classes with them or they’re not my friends, I’m more likely to smoke because of this social effect that started with a spark from their genes. And that effect is so big that it’s almost as big as the genes of my own body determining whether I smoke or not.

Paul Rand: One of the disturbing trends of all this is that society is starting to naturally sort itself by genetics. The main way this is happening is through our love lives.

Dalton Conley: Yeah, it’s interesting because hundreds of years ago, we lived in small villages and most of us did somebody who is, if not literally, our cousin, someone who could easily be traced to our same family tree. In the contemporary US, we think of ourselves as so far from that, that village clannish approach to reproduction. You literally can swipe through an almost infinite amount of potential mates on these online apps today. Ironically, because we have so much choice, we end up choosing people who are genetically more similar to us. So across the entire genome, spouses are as genetically similar as second cousins. When you get to specific polygenic indices, specific genetic signatures for something, for education, we’re more like first cousins marrying each other. And for height, we’re more like half siblings.

Paul Rand: But our genes aren’t just sorting us through our relationships. Some polygenic scores seem to cluster by state, politics or economics. Studies that looked at declining factory towns in Appalachia found that people with high PGIs for education were more likely to leave while people with lower PGIs were more likely to stay.

Dalton Conley: We’re sorting so much that we end up making ourselves much more genetically similar to our spouses than we would be to a random person in society. And that in turn has implications for how much inequality there’s going to be the next generation.

Paul Rand: Demographic estimates have shown that increasing sorting among US spouses in terms of economic factors could explain up to 40% of the rise in income inequality in recent decades. And this is only going to get worse as these technologies become more available.

Dalton Conley: One of the more possible applications is you download your raw data, you upload it into this dating app that’s piggybacks on Tinder or Hinge or whatever the hot one is now. It calculates and displays your certified polygenic scores for a variety of traits, along with your photos and your description of how you love cats and dogs or whatever, and people have that information. And the dating... Maybe only nerds would go for that dating site, but I think that would be more than a novelty as this seeps into society. Most people don’t know about polygenic indices right now, but I think that’s going to change in the next few years.

Paul Rand: So how close are we to a dating app that’s driven by polygenetic influence this year?

Dalton Conley: We literally could be there tomorrow if all the pieces are in place, which leads us to another discussion about how these polygenic indices are going to be used in society once they break out of the lab.

Paul Rand: So what does the future look like when these polygenic indices break out of the lab? Well, that’s after the break.

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If you think about it may actually influence society, policy, other things, where does that take you in your thinking and the upside or the downside of that?

Dalton Conley: Yeah, I mean, there’s a lot of important policy questions that come out of this new world, this social genomics revolution I call it. Just to take a few examples, we have to make certain decisions about insurance markets, about schools and so forth, ova and sperm donor banks. So for example, right now, it is a hundred percent legal for a fertility clinic to sample embryos. If you ended up with a dozen viable embryos, there are companies now that will extract DNA from each of those 12 embryos and calculate the polygenic scores of each embryo and then allow you to decide which one to implant based on that information. There’s a bunch of babies already born. The first one was born in 2020 that have been polygenically optimized, so to speak. So there are fertility clinics doing this now.

We are the wild west when it comes to fertility medicine. Other countries, I think France for example, doesn’t even let you choose the sex of your offspring, even though that’s pretty routine in the US. And so there’s really no regulation. And that might be fine. We might want to let people do what they want with this new technology in the fertility clinic, even though it’s very early echoing of the movie Gattaca in 1997, which literally is... Yeah, this is literally Gattaca has arrived, where there’s a new cast of people that were optimized genetically, and then there’s Ethan Hawks, the protagonist, plays the protagonist who was conceived the old-fashioned way and doesn’t have the genetic quotient of his brother.

Paul Rand: I mean, you kind of get to the point where a lot of scientific insights and breakthroughs happen, and there’s what we found this, it’s up to society to determine what it does with it, which is always one of those really challenging considerations. What are you excited about and what are you really fearful about based on this insight?

Dalton Conley: That’s a really tough provocative question because I try to avoid taking a stand on any of these things, but you’re forcing me to. I guess I think it seems very reasonable and low hanging fruit that we would test sperm and over donors and just provide that information about the polygenic scores to the potential recipients of those donor eggs or sperm. There’s undoubtedly ethical issues involved there, but that seems like one of the more straightforward use cases. Do I think that car insurance companies, life insurance companies, long-term care insurance companies, which are all not prohibited by the genetic information, non-discriminatory-

Paul Rand: They’re not prohibited today?

Dalton Conley: Yeah. There’s only one law that’s at a national level that regulates how we can use personal genetic data, and that’s GINA, Genetic Information Nondiscrimination Act of 2008 signed by George Bush. And it prohibits the use of genetic information for healthcare and health insurance and employment decisions, but that doesn’t apply to car insurance, life insurance, long-term care insurance. And with an aging population, that’s going to be increasingly a bigger and bigger market.

So if I were an insurance executive, I would start by offering a discount to anyone who would provide a sample or their data, and then I could train my models and risk adjust based on the polygenic score for risk-taking, behavior, addiction, alcohol use. I would bet my life savings that would predict car accidents and I can then adjust my premiums that I’m going to charge based on this information. When my then 18-year-old son applied for car insurance and asked whether he was in a frat, it asked his GPA, it asked all these questions that obviously some machine learning algorithm said were predictive, and I would say that the polygenic indices are going to be even more predictive and would save insurance companies money.

Do we want to allow that for long-term care as well? Well, we’ll start to... If we don’t, then maybe people actually assess their own genetic risk for dementia, let’s say, and only the people who are at very high risk by long-term care insurance. And then you have what is called a death spiral in the insurance markets because the prices keep going up because only the ones who are at risk by it, and that drives a forward-feeding cycle until the market collapses.

So we have tough choices to make. It’s not so simple just to expand GINA to these other insurance domains because then you’ll have this asymmetry of information where individual, consumers might have the genetic information and make decisions based on whether to buy insurance or how much insurance to buy based on that information. And the insurance companies won’t be able to adjust prices accordingly and they’ll end up collapsing the market. So that’s one possible scenario. I’m just saying it’s hard to put this genetic genie back in the bottle now that we-

Paul Rand: We can have schools that are for people of certain polygenetic scores.

Dalton Conley: Right. That’s a domain I maybe worry about the most because right now, the educational attainment, as I mentioned before, is 40% heritable and the polygenic score only predicts about 16 to 20%. But imagine schools that admit students or track students based on that score, it’s going to end up rising in its predictive power because it’s going to structure their whole educational experience. And then we’re going to get close to, I don’t know about 100%, but it’s going to get into the realm of dystopia where we’re making a self-fulfilling prophecy.

There was a very famous study in the 1960s called Pygmalion in the classroom, where they lied to teachers and they randomly told them that these five kids in your class tested in this really awesome cognitive test that’s really predictive of educational success and they’re geniuses. And there was no test. They just trick the teachers. And those kids’ IQs actually went up, I think by 10 points in a year because they were treated differently. So the environment still matters a lot. So I’m afraid that we’re going to create some quick, crazy genocast society if we don’t have a careful dialogue and public education about this.

Paul Rand: So most of the genomic studies, if I remember, it was like 85% were done on populations of European ancestry. Why is that and what implications does that have?

Dalton Conley: Yeah, that’s a really important point that we haven’t discussed yet, which is that whether this is a useful tool, it’s going to lead to a utopia or it’s going to lead to a dystopia like we’ve been talking about. Whatever that is, it’s going to be currently for white people only, white non-Hispanics, because the polygenic scores have been trained to predict for people of exclusively European descent, and they work the best for people of exclusively European descent, and they do not predict well, they’re noisy and they’re in fact biased in predicting for other groups like Asians or predominantly African descent or Latinos who have a lot of Native American ancestry in their DNA.

The reasons for this, scientists are still trying to work out what they call the portability problem, why you can’t port a PGI from one population to another and have it work. Is it because of different environments? Is it because of different genetic architectures in the populations? And that’s a really technical thing to get into, but the bottom line is they don’t work. So if the PGI is going to be used to screen for early treatment for cardiovascular disease, which they are being used, I think, in the UK that way already, if someone is very high on the cardiovascular disease polygenic index, they start them on statins and other preventative measures very early in life before plaque starts forming their arteries, that’s a really good use. That seems like maybe the least controversial use of these and the most beneficial. Yet, is that only going to be for white Americans and not for Black or Latino Americans? I don’t know. I think we need a massive data collection effort to develop scores in these other populations.

Paul Rand: Is that happening?

Dalton Conley: Very slowly. I mean, the reason we have more information and more better scores for people of European descent is because a lot of the data comes from Europe and from countries like the US that’s majority people of exclusively European descent. Australia, Canada, Northern Europe, those are the rich countries that are able to do this. They are predominantly white and they end up with those scores. So there is a massive effort in Asia, in East Asia and China and Japan to collect data and run analyses, and there’s an effort ongoing in Africa to where actually there is the most genetically diverse population in the world is in sub-Saharan Africa, yet we have very little data there, but it’s going to take a lot more investment, and I’m not seeing that come from the public sector in the US in any time in the near future.

Paul Rand: There’s not a person listening that’s not thinking, “I’d like to go get my score, my polygenic index score.” How far off can you say I’m going to go to Walgreens and get my score?

Dalton Conley: I think we’re just one startup away from that, basically. Yeah. All the pieces are in place that people could do that. I mean, right now-

Paul Rand: When does Elizabeth Holmes get out, by the way?

Dalton Conley: I don’t know.

Paul Rand: That would be good.

Dalton Conley: I wouldn’t buy her kit. But yeah, you could do... 23andMe is gone now, but you could do ancestry.com. You could download your raw data, and I think there used to be, and I don’t know if there’s still active sites at which you could upload that raw data and it’ll calculate your polygenic indices for you. That’s a lot of steps. Most people probably want to go to Walgreens, like they get a COVID at home test and swab themselves and then mail it in, or maybe there’s going to be some day when it can just be transmitted the data to them wirelessly and get your scores back.

Paul Rand: We’ve toyed around the edges on this, but if we’re thinking 10 years out, startup-wise, otherwise, what are you thinking we’re going to see will have evolved during that period of time? Particularly as you mentioned with AI coming into the mix, whether it’s actually faster computers that are helping us get there, but the speed of discovery here is likely to be going up exponentially.

Dalton Conley: I think the scores are going to get better to a certain extent as we get more data. That’s really... I don’t think it’s the computational techniques of AI as much as we need more data and we need structure in a certain way that’s collected with family, entire families, for example. And the UK is moving forward with that. I don’t see us doing that. I mean, we weren’t already, and certainly now with NIH funding cuts, I don’t think that’s going to happen.

I think there are some upper limits too. So what we’re going to be able to predict because there’s, of course, the genetic component of, for some cases, if you want to predict your spouse’s or let’s say your child’s personality type, that’s much more influenced by environment and not that genetic. So the score for, say, neuroticism or extraversion is going have a very low upper bound or ceiling that it can reach. So much of the effects of the genes work for the things we care about, like the social things we talked about, income and education work through the environment. The good news about that, let’s say cognitive ability that’s 75% genetic, since it’s working through the environment and not just stopping at your neurons or the edge of your cranium, it means that we can do something about.

Paul Rand: As we peer into a future shaped by genetics, kindly reminds us that it’s not about choosing between nature and nurture. It’s about understanding how our genetic blueprint interacts with the environments that we create, and perhaps most importantly, recognizing that while genes can predict our potential, it’s up to us to shape the world in which that potential is realized.

Dalton Conley: We could provide those environments, those enriching environments. You’re wearing glasses. Myopia is one of the most heritable traits there is, yet is it got an easy fit environmental fix is that we just distribute classes. That’s a classic example. So I don’t want people to come away from this hour thinking that, “Wow, it’s all in our genes. There’s nothing we can do about it.” The whole point of the book is that a lot’s in our genes, but there’s a lot we can do about it because the genes work. Don’t stop at the board of your skin.

Paul Rand: It’s nature and nurture.

Dalton Conley: Yeah.

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