Popular Genetics: How Learning About Our Genes Offers Both Benefits and Limitations

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00:00 Mike Boehnke: Public health is about the public's health. We're interested in learning the basis of human health and disease. We're always trying to do what we can to improve human health at a population level. To do that, we need to pay attention to the different determinants of health, and there are lots of determinants of health that aren't genetic but certainly, genetics is part of the picture. Genetics also has the advantage that it's relatively simple. Three billion base pairs is what you get in terms of genetic material, that's finite and it's largely fixed. And so it gives us an entry point to understand human health and disease. It gives us a way to go about studying human health and disease, that in the broader context of all the different things we do in public health in terms of people's behavior, in terms of the environment, that genetic component is a piece of the puzzle, a part of the picture that we need to look at as we're doing our best to improve the public's health.

01:04 Speaker 2: The study of genetics in public health goes much deeper than exploring why someone has blue eyes, or brown hair, or why someone's tall or short. Over the past generation or two, knowledge about DNA has entered the zeitgeist in part due to criminal investigations and celebrity trials. In these cases, the focus is often on the individual and not the larger population. So it may be a little surprising that the building blocks of genetics, DNA, genes and chromosomes passed down to you from your parents, have been an area of focus in public health for just as long.

01:40 S2: Hello and welcome to Population Healthy, a podcast from the University of Michigan School of Public Health. Join us as we dig into important public health topics, stuff that affects the health of all of us at a population level. From the microscopic to the macro-economic, the social to the environmental. From neighborhoods to cities, states to countries, and around the world.

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02:13 S2: In public health, studying genetics is key to understanding a population's likelihood to contract certain diseases so that steps can be taken to mitigate that risk. On a more individual level, people now have more options than ever for learning about their own genetic makeup and how their genes affect their health, but there are benefits and limitations to all of this. Today, we'll explore these topics as we talk to three researchers whose work focuses on different areas related to the field of genetics. To get started, here's a quick refresher on our genes and how they work.

02:48 MB: Hi, I'm Mike Boehnke from the Department of Biostatistics at the University of Michigan School of Public Health. So gene's the basic unit of heredity, it's what passes from parents to offspring that codes for the traits, the characteristics that make us human, or for other animals, or plants, or whatever they might be. They determine observable characteristics like eye color, they determine measurable characteristics like your height, and they also predispose to human disease or make a difference in our risk to human disease. In some cases what we call simple Mendelian disorders, where one bad gene or two bad genes can give you a disease.

03:23 MB: In other cases, common diseases, typically, like type 2 diabetes or various forms of cancer, typically it's multiple genes that are involved in the interplay of those genes and interplay with the environment. A gene is actually a sequence of nucleotides within a chromosome. The gene is used as machinery by the cell to be transcribed to RNA, RNA is then translated to proteins, and so basically genes indirectly in that path code for proteins. And since proteins are sort of the building blocks of cells and orchestrate a lot of what goes on in cells through the actions of enzymes, which are proteins, genes are really the information transfer that allows us to build cells, build organisms, build you and I. So, it's a blueprint in the sense that it gives the fundamental genetic information, which is a substantial part of who and what we are, but it's only part of who and what we are. Because what we do, the kind of lifestyle we live, the kind of raising we get from our parents, all the other things that go on as a human grows and develops and becomes whatever she or he might be, the genetics is part of the basis for that but only part. The chromosome is one of the, in the case of humans, 46 entities that carry the genes and a bunch of other stuff.

04:39 MB: It was actually an interesting thing we learned when the genome was sequenced, and actually knew some before that, but as we got more and more information about the human genome, the 46 chromosomes have about 2% of their content that actually codes for genes. There's a fair amount more that's actually responsible for how those genes are expressed, and then there's a fair amount more beyond that we just don't even know what it does.

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05:08 S2: Which brings us to some of the exciting frontiers of genetics in public health. Remember, we all have about 20,000 genes. To get a deeper understanding about human health researchers at the University of Michigan School of Public Health are working to understand them and how very specific interventions may prevent or curtail disease.

05:29 MB: When, in about 2006, we carried our first genome-wide association study for type 2 diabetes, a gene called SLC30A8, which is actually a gene that's responsible for transport of zinc to the beta cells of the pancreas. And SLC30A8, and in a particular a single misspelling in that gene, led to about a 10% change in risk for type 2 diabetes. This was one of the first genes that we identified, one of the first 10 that we identified as being important. And that was sort of interesting because it was a misspelling that actually caused a single change in the protein, a change in the amino acid at one particular location, and given that it's something that was specific to the beta cells of the pancreas. I'm not a great diabetes biologist, but even I knew that beta cells of the pancreas are the tissue that produce insulin. And so something that might be important in transport in this really critical tissue, and then possibly being a relevant risk to type 2 diabetes, that seemed pretty exciting.

06:30 MB: Since then, colleagues of ours at the Broad Institute, us helping out, others helping out, looked at a much larger number of people in a much more detailed way, actually sequencing this gene in about 150,000 people, and found that more severe modifications of this gene, what we would think of as mutations, and mutations that didn't just change a single letter of the alphabet, but actually caused the protein product to be truncated and therefore probably not active, that can actually lead to a three-fold decrease in risk to type 2 diabetes. Now, a three-fold decrease is a pretty big deal. I look to try to find the genetic basis of human health and disease, partly because it's just fun and it's an interesting puzzle, but honestly, a major reason for doing it and honestly why the government is happy to fund it and should be happy to fund it is that we might be able to identify possible new therapies. And this is a promising one.

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07:23 MB: We've been doing the genetics of type 2 diabetes long enough to know that it's hard. Diabetes is a really complex disease and we know that there's a lot more going on besides genetics. Genetics is only a small part. Behavior, what you eat, what your lifestyle is like in terms of physical activity, those are really important. And so we said, "We wanna work together with other people," because this new technology we had available to this genome-wide association study we thought gave us a chance to be successful. But we knew if we had not just our study, but other studies working together, we'd have a greater chance of being successful. And so we brought together three different groups, ours and two others, who decided that we would share our data right from the very start.

08:04 MB: And when we did, we ended up with a list of nine places in the genome where there were factors predisposing to type 2 diabetes. Without that sharing of information, we would have had maybe one or two, and those basically already known. At the start and at the end, in human genetics, we want to be sharing information, bringing information together for our discoveries, taking the information and broadcasting it as broadly as we reasonably can to other scientists who might be able to take advantage of it.

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08:35 MB: We can sequence a human genome in a matter of hours at a cost of about $1,000, in comparison to the Genome Project, where for several years we paid something like a billion dollars to effectively sequence one genome, actually sort of a composite genome. You don't have to be brilliant, when you see that kind of fundamental change in what's possible, to go and do something good with it. I was lucky enough, and my colleagues working together, we were lucky enough to be working at a time when these remarkable transformations happened that enabled the kinds of studies that I knew I wanted to do back in the early '80s, but didn't have a prayer to do for the kinds of diseases we study now.

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09:24 S2: So the study of your personal genetics tells us about you, but it also tells us about your history, namely, your ancestors. And if we know more about your ancestors we also know a lot more about patterns in human health. And if we know that, we may be able to project into the future about our risk for disease. Now, unless you are a genetic epidemiologist, the work of this next researcher will be new to you.

09:49 Sebastian Zoellner: I'm Sebastian Zoellner, Professor of Biostatistics in the University of Michigan School of Public Health and Professor of Psychiatry at Michigan Medicine. My work is at the intersection of population genetics and genetic epidemiology. I'm trying to understand how the history of a population affects the patterns we see in modern genetic data and how we can use that history to understand how genetic information affects our risk of diseases.

10:15 SZ: If you want to understand the history based on genetic data, you can obviously go and find genetic data from a 1,000 years ago, 10,000 years ago, you can look at the genetics of the Neanderthal. But you can also just look at present-day genetic data. And the idea here is that if you compare the genetic information between two individuals, that how different they are is a reflection of their past. If you, for example, take the genetic information of two closely related individuals, you'll find it's in some areas very similar, reflecting that they have a common ancestor very recently, say the same grandfather. But if on the other hand, you take two random individuals and you compare their genetic information, you'll see it's reasonably different and that reflects a more distant ancestor.

11:01 SZ: So this way you can tell how far back in time the two individuals have a common ancestor, and that tells you about the history of the population. If we talk about genetic information, remember that only about 1% of the genome actually codes for proteins. 99% of the genome have either regulatory function, or have no function that's particularly beneficial to humans. But all of that carries information about the history, because what we care about is not the functional changes that make us into who we are as beings, but just random changes that accumulated over time. Those are the ones that give us information about the history of a population. Actually there's quite a bit of information available only within the genetic data, so you can compare and you can basically cluster individuals by how similar they are to each other. If you, say, take a sample of Europeans, you get a two-dimensional structure of which populations are close to each other, which populations are far away from each other, that reasonably well recapitulates the European map. So if you turn and twist that, you actually get the European map back, just based on how similar those people are. You need no outside information for that.

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12:05 SZ: When modern humans came into the world, they have interacted, interbred with the previous hominids there and they've also kept the DNA that was useful and pretty much rejected the DNA that was useless. So really a nice story there. If you go into Tibet, you'll find that the people there are extremely adapted to living at high heights. Turns out that's a gene they got from the local equivalent of Neanderthal and maintained it because that lived there way longer than them and they had actually the time to adapt.

12:35 SZ: Another cool story is lactose intolerance. It's one of the basic examples that always gets used when we talk about selection because as you probably know the historical state, the ancestral state, is lactose intolerance. Lactose tolerance is something that arises in a population with a lot of dairy production because the gene that is designed to turn off your ability to metabolize lactose breaks. And if you have a lot of cows around, that's good if that gene is broken because suddenly you can use the milk, right? And the interesting thing is that actually happened multiple times in the history of human kind. It happened in Europeans and that's why Europeans are typically not lactose intolerant, but it also happened in East Africa. Same gene, broken in a different position because they were also a cattle-keeping society and so they also had an advantage if they were lactose tolerant.

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13:26 SZ: One of the questions that clearly motivates a lot of my research right now is improving the equity in genetic research. For a lot of very valid technical reasons, the first 10 years of genetic research have been heavily focused on only using one population, right? Because homogeneity is useful if you do research. And of course, it was the population where we had the most data, the most money, people of European decent. That has the problem that it increases already existing health inequities. So right now, the research is moving in the direction of using more African American samples, Latino samples. But the problem here is, of course, also the machinery that we use to analyze all of this has developed to analyze the data we have and not the data we're getting, so now we need to think about how can we adapt the existing machinery to analyze these new, diverse samples.

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14:21 S2: While one new frontier in genetics is about the diversity of our genetic research, another relates to how a growing number of people may interact or confront their own genetic information. If you've ever received a genetic testing kit as a birthday present you might know what I'm talking about. The prospect of exploring your own genetic makeup is exciting, but the information that comes back can be difficult to understand and perhaps even scary. Scott Roberts, a professor of Health Behavior and Health Education at the University of Michigan School of Public Health, is here to discuss the wide spectrum of ethics and implications of personal and direct-to-consumer genetic testing.

15:00 Scott Roberts: My research interests are focused on how people respond to learning genetic risk information for various diseases. I think what scares some people about genetics and the use of genetic information is based on, I think, a troubled history of how genetics has been used in the past. So everything from Nazi Germany trying to promote this master Aryan race, but even here in the United States, we had a very troubled history. Eugenics was behind a policy of forced sterilization of people who were called feeble-minded and so that actually took place over several decades, into the 1970s even. We've had troubles with genetics research, people know the Tuskegee study, which was actually based on this notion that African Americans were somehow innately biologically different and therefore we needed to see how syphilis occurred in black bodies was the idea. And I think in present day, we see lot of wariness around genetic privacy. Popular culture feeds a lot of this too, I think, in the media, so there's all kinds of dystopian fiction out there based on these nightmare scenarios of scientists run amok.

16:15 SR: And so, I think this combination of factors may help influence some people's wariness about the use of genetic information. In terms of the misuse of genetic technology, some of the modern day concerns are that we might see the use of genetic testing expanding too much before it's ready for prime time. It's very easy now just from a saliva sample even to get even a whole genome sequence. And so I think there's concern that we might go too fast too far in using genetic testing.

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16:51 SR: So there are a lot of potential risks and harms of providing people with genetic information that, at least in theory, exists. So one major risk is psychological distress. Genetic information, when it's being provided for example, for maybe risk of a severe, incurable condition like Huntington's disease, can be very distressing. And so, people often stay away from that information, they may choose not to even sign up for genetic testing of that kind in the first place. But I think there's the fear that if people aren't prepared to learn this kind of information, it could be very upsetting to them. There's also a lot of concerns around genetic privacy, fears of genetic discrimination.

17:32 SR: So if genetic risk information for various health conditions gets in the hands of insurers, employers, criminal justice system, there's potential for misuse of that. So I don't think the actual level of genetic discrimination is very high in this country, but understandably, people are still worried about the possibility. So to mitigate these potential risks on the psychological distress side, I think we can pay attention to really good genetic education and counseling. And in fact, there's a whole field of genetic counseling that provides training to clinicians and if it's in a healthcare context, providing this upfront education to prepare people, to make sure that they know what they are gonna receive in terms of information, and to decide, do they even really want this testing at this point in time? 

18:21 SR: But even beyond just formal genetic counseling, I think there's a lot of ways we can support genetic education so that people are really giving truly informed consent to genetic tests that they may undergo. I think in terms of these genetic discrimination risks, we do fortunately have some laws on the books that protect against genetic discrimination. So back in 2008, this federal law known as GINA, The Genetic Information Nondiscrimination Act, was passed. And so that prohibits employers or health insurers from using genetic information, for example, in any kind of hiring decisions or insurance decisions about setting of premiums, that kind of thing. I think it's also important though to point out that GINA does not cover life, disability, or long-term care insurance, so some people have suggested we should have a follow-up amendment to that policy to expand that protection.

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19:19 SR: Consumer genetic testing refers to this idea that we have many more companies out there developing and offering genetic testing services, both in the context of healthcare, but there's been a lot of growth in this industry known as direct to consumer genetic testing, which can be provided in a variety of ways and for a variety of reasons. There are some companies, like 23andMe, that many people have heard about that offer health-related information. There's other companies that focus on genetic ancestry, there's some that provide genetic testing around fitness and diet. There's different options here. We've seen this really grow in the past decade and so there's a lot of excitement in that area, but then from the public health side, some concerns about do we need to more tightly regulate this growing industry? Are they really offering tests that do what they say they do and that provide true benefit to people? The concerns about companies like 23andMe in terms of the risks involved, this issue of psychological distress as a potential harm, most direct to consumer companies are providing a lot of different genetic information for a lot of different health issues and they're not necessarily getting truly informed consent upfront.

20:36 SR: People are not meeting with any kind of clinician to discuss this testing ahead of time. So there's the fear that people might be blindsided by information they weren't really aware they were going to get. And so, 23andMe for example, includes health risk testing for conditions like Parkinson's, Alzheimer's. So those are pretty serious diseases that people, in theory, could get troubling information that they're not prepared for. On the other hand, I think we've actually done some research basically suggesting that the likelihood of those kinds of reactions is very low, that even though I think in the ethics community those concerns have been raised, we haven't in real practice seen this really happen that frequently. Another concern is that people may take direct to consumer genetic testing results to their primary care physicians for interpretation, but that that's not necessarily the best use of their limited time for interaction with their primary care doc.

21:35 SR: Another potential risk is some companies provide direct to consumer testing and give you access to a raw data file that you can then take and use in other ways if you'd like. And so there's now these third-party testing companies popping up on the web, so people are taking, for example, their raw data from a company like 23andMe, inputting it into this third party site, and there have been some case examples where that third party testing has resulted in people being alarmed they may be at high risk for Alzheimer's or breast cancer, and it turns out that that really wasn't the case, that this unregulated third-party testing was giving them erroneous results.

22:19 SR: So I don't think that's very commonplace, but again, the more you are doing genetic tests for multiple conditions at once, the higher the likelihood there could be some kind of error or false positive that could provide unnecessary concern and distress. I think this is becoming a big issue because some of these companies, they now have a customer bases in the several million and that's just in a relatively short period of time, and so I think we're seeing much more use, access to, awareness of genetic information at the personal level, so I think that's why the time is right for us to really think through, how can we structure a regulatory system? How do we educate the public? How do we think about uses within formal healthcare systems and beyond to really harness this technology in the most effective way? 

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23:24 S2: Thank you for listening to this episode of Population Healthy from the University of Michigan School of Public Health. We're glad you decided to join us, and hope you learned something that will help you improve your own health or make the world a healthier place. If you enjoyed the show, please subscribe or follow this podcast on iTunes, Apple Podcast, Google Play, Stitcher, Spotify, or wherever you listen to podcasts. Be sure to follow us at UMichSPH on Twitter, Instagram and Facebook so you can share your perspectives on the issues we discuss, learn more from Michigan public health experts, and share episodes of the podcast with your friends on social media. You can also check out the show notes at our website, population-healthy.com for more resources on the topics discussed in this episode. We hope you join us for next week's episode, where we'll dig further into public health topics that affect all of us at a population level.