Okay. Hello. Unit 8. So we're on the home stretch now. This is the final unit of this course, I don't know what I'll do after it's over. The, what I'm going to do in this unit is I'm, I'm actually going to begin with a summary. Kind of a big picture of what I was trying to achieve. 20 years from now, what you should really be remembering maybe, from this course. And then I'm going to use the, the remaining three or four modules to be a little more speculative about this area of science and how it might impact things like public policy or the law. So, but today, I'm going to begin with a summary. And the way I'm going to frame the summary is actually by, around an article that was published in 2000 by this individual, Eric Turkheimer, who is a behavioral geneticist at the University of Virginia. And the title of the article is 3 Laws of Behavioral Genetics. And he published it in 2000 and here are the three laws, I'm going to come back to those in a second. And I think it's a very effective summary of the major findings of behavioral genetics. What are the major things that behavioral genetics has contributed to the field of psychology, that almost all psychology acknowledges? These are his three laws, but of course I've got four laws listed up here. Where is the fourth one coming from? Well the fourth one is coming from a young colleague of mine here at the University of Minnesota, and named James Lee, who's also a behavior geneticist and, and James is, is publishing an article called The Fourth Law of Behavioral Genetics. So I'm adding in his fourth law there, because I think it's a very important addition to what Eric did back in 2000. So, what are the four laws? All behavioral traits are, in part, heritable, the shared family environment doesn't seem to have a big impact on behavior. The third is environment is very important but appears to be the non-shared environment that's most important. And finally, that behavioral traits appear to be highly polygenic. That fourth one being contributed by James Lee and actually a colleague of his, named that we talked about earlier in the course as well a man named Chris Shipley. So, let's talk a little bit about that first law. All human behavioral traits are heritable. That first law deals with (A). And in fact, if you look at those first three laws that Turkheimer gave us They deal with A, C, and E. Those three letters that hopefully now are ingrained in your mind. A certainly ingrained in behavioral geneticist's mind. So what did we learn, or what I hope you learned big picture about the heritability of behavior. First of all the association with early behavior genetics with the Eugenics Movement led to psychology rejecting genetic explanations early on. In my opinion, and it's nothing more than that, in my opinion, that really, really delayed the development of the field of psychology in very important ways. We went off on tangents, we looked for skitzophrenogenic mothers, or refrigerator parents when no such individuals existed. And it wasn't until we came back to the 70, and to be able to genetic research in the 1970's. And later that we really began to understand the complexity of individual differences and behavior. So that's the first thing I hope you remember. The second is that the conclusion that behavior is heritable isn't based on one particular study certainly or even one particular type of study. We have twin studies, we have adoptions studies, we have studies of reared apart twins, we have family studies, we have candidate genes, we have GY studies, we have all different types of studies that are all telling us that behavior is heritable. It's not perfectly heritable, but it's heritable. The third thing is that for some traits, and I gave you a couple of these: general cognitive ability, rule breaking behavior, our social attitudes. And there are others, things like our weight, our BMI, body mass index or obesity. The heritability of these traits increases with age. And in particular, increases during the transition from late adolescence to early adulthood. Behavioral geneticists hypothesis that an increase inherit ability with age owes to the importance of gene environment correlation, in particular active gene environment correlation. That as we get older one thing that happens is we gain greater control over the activities we engage in. And when we exert that control we're likely to exert that control that reinforces inherited tendencies, abilities, interests. Finally the fourth thing I hope you remember about the heritability of behavior is that, the heritability of behavior isn't fixed, that it varies. I guess gene environment correlation is one way it varies, it varies across development but it also varies in cross environmental cons, con, contexts. That's gene environment interactions. And we saw various types of gene environmental interactions. Two very prominent types, impoverish environments can limit genetic influences on desirable traits. We saw that on general cognitive ability. The heritability of general cognitive ability, is much lower in an impoverished environment, than in an enriched environment. Secondly, protective environments can minimize, the impact of genetic influence. We saw that with aggressive behavior in children. If they're reared in a protective or nurturing environment that genetic influence on aggression appeared to be diminished. The second law is that the shared environment appears to have minimal impact on individual differences in behavior. In my opinion, this is the most remarkable finding to come out of behavioral genetic research, because most of us think just the opposite, that we are shaped by the families we grew up in. This second law refers to C, the shared environment. Just like the conclusion that heritability of behavior exist, the conclusion that the shared environment doesn't appear to be very important for most psychological traits is a reflection of a convergence of evidence across multiple lines of studies. MZ twins are at least twice as similar as DZ twins something we talked about last week when we talked about personality research and the Faulkner model, the Faulkner way of estimating A and C. Reared-apart twins aren't much less similar than reared-together twins. And those adopted siblings, individuals who aren't genetically related to one another, placed in infancy in the same home, are they psychologically similar? Not very psychologically similar. those all seem to be telling us that the shared environment is not that important. Now I also noted that their are some traits for which the shared environment is clearly important. General cognitive ability, rule-breaking behavior, social attitudes. And I pointed out that, if you think about it, these are the types of traits that are very important to parents, so maybe that makes sense. But even when these traits are important, er, er, I'm sorry, when they show a shared environmental effect,. The magnitude of that shared environmental effect appears to decrease with age. In particular, decreases during that transition from late adolescence to early adulthood. Finally, the thing that I, I recognize this is a little bit too obscure, but it's important to emphasize. The absence of what behavioral geneticists call shared environmental effects really means that families don't appear to be shaping the children growing up in those families in a similar way. It isn't the same thing as saying the families have no effect. Rather, families might have a large effect but they might be affecting the children in the families differently. Like, divorce might affect different individuals in the family differently, depending on their personality, maybe their gender or how old they were when the divorce happened. To the extent that happens that's not a shared environmental effect, if it's effecting individuals differently. That would be, the third type of environmental effect, a non-shared environmental effect. The third law, the non-shared environment exerts a major influence on individual differences and behavior. This is E. We know E exists because E reflects differences in Monozygotic twins. Monozygotic twins have the same genome. They are reared in the same environment so they share all those A effects, all those C effects. So if they're phenotypically different, it has to be their environments it has to be their non-shared environments. And one of the things I've emphasized throughout is, Monozygotic twins as a group are never perfectly correlated are never perfectly concordant for behavioral characteristics. We know that the non-shared, the E effects are there. Well one of the things I pointed out is that when the biometricians estimate the E effects, it includes measurement error. And psychological traits are measured with some error. You measure my personality today, you measure it on a beautiful summer day, it's going to be a little bit different. That's measurement error. And most estimates of measurement error for things like personality say that about 10-15% of the variance is due to just the limitations of psychological measurement. That comes out of the E component. That means for a trait like general cognitive ability, where the E estimate is about 15%, might mean that there aren't powerful non-shared environmental effects for general cognitive ability. But for something like personality, where the E estimates were on the order of 40 or 50%, there is still a lot to be explained there. Which leads me to the last point about E. What are the, if it's such an important effect, what are those effects that really shape, environmentally shape our psychologies to be different? We talked a little bit about in schizophrenia that the important environmental effects certainly are the non-shared in variety, and they appear to be related to early neural trauma. But what about personality or other psychological traits? So lets take personality. What makes me neurotic and you, not neurotic. Or what makes someone outgoing and another person withdrawn? What about our environments? I don't know that psychologists can actually tell us what are environments that actually lead some people to be sociable, or anxious, or timid, or obsessive. There non-shared environmental effects but we actually haven't done a great job identifying what specific factors those facts refer to. The article you're going to read by Turkheimer talks about what he calls and what others have called the gloomy prospect. And the gloomy prospect is basically this, what makes me neurotic is completely different from what makes you neurotic. It's very idiosyncratic, it's some odd thing that happened early in my life and you have a, a whole set of different factors that make you neurotic, and so we can never really try to understand at a population level. We're kind of reduced to biography, because each person comes to neuroticism in a different way. And that's rather gloomy for psychology, maybe great for the biographers but not so good for a psychologist. The fourth law, Human behavioral traits are polygenic. This is something that Turkheimer really couldn't have commented on back in 2000, but James Lee and Chris Chabris can today. The polygenic nature of behavior. Candidate gene studies were premised on the beliefs that we could pick the right genes and then that we could get a large enough sample to identify the variants in those genes. We know now that, there, there's not really a fundamental flaw in doing candidate-gene studies. It's just that when we tried to do them in the 90s and the early 2000s, we really didn't have large enough samples and we really didn't know which genes to pick. Now, since 2007, we can do genome-wide association studies. We've talked a lot about that in this course. And when we've done these, for trait after trait, behavioral as well as non-behavioral, there's nothing really unique to behavior here, we find three things. The effects of the variance we identify in those studies are small, very, very small. If the effects are small, then there must be many, many of them underlying the heritability of those traits. And in fact, the estimates of the number of genetic variants underlying schizophrenia, or bipolar disorder, or general cognitive ability aren't 10, 20, 100, or even 1,000. The estimates are there are thousands of variants out there to be identified. Because we've only identified a small number and there are thousands that are likely to be contributing most of the heritability is missing. This has led some to really question whether or not it's worthwhile to do genome wide association studies. These are two quotes from two very prominent, reasearch group. Tim Crow is a very prominent schizophrenia researcher McClellan, Mary, Claire King is a very prominent human geneticist. She was very much, involved in the, the, the identification of the breast cancer genes. And both of them are really, arguing here, and I'm not going to go through the quotes, you can read them if you'd like, but I tried to highlight what, what they're arguing, is that gee, you're finding these very small effects, is it even worthwhile to do this? It requires extraordinarily large samples, lots of resources, why bother? Why bother? Are you really getting anything for our money and for all our effort here? They're saying we're not really getting it. Now, this again my opinion,. You might, these are very prominent people, I'm sure they're much smarter than me. And you may at the end of this course, I'm fine with that, say, yeah, I think they're right. But there are other people that, myself included, that think there really is something worthwhile going on here. So what are the pro arguments for GWAS? Well as samples get larger and of course they're getting, they're needing to get very much larger, we're finding more and more variance. A few years ago, we couldn't find anything with schizophrenia we talked about a study in schizophrenia in this course that I think it was something like 22 variance were identified. Of course it took a long, large sample you double that sample maybe you find seventy variants and so on and so forth. Believe it or not, for all its limitations, GWAS has a better track work record than candidate-gene studies. We did candidate-gene studies for 15 years I'm not sure we got a lot out of it, in my opinion. Finally, and here's the major argument, counter argument to the pre, two previous quotes. That even if the effects are small, they provide some very important biological insights into the path of physiology of these disorders. And I'm going to try to highlight this with a gene that was identified for obesity. Last time actually, I highlighted it with genes that who are identified for Alzheimer disease that have, even though they have a small effect, have provided some insights into the path of physiology of that disorder. But in this case I'm going to talk about a gene called the FTO gene. What FTO stands for is actually not that important here. FTO, a, a genetic variant in FTO was identified in a GWAS study in 2007 as being associated with obesity. And you can see that, actually here i plotted a number of publications about this variant and obesity since the initial discovery and you can see there's a lot of research going on in this particular area. It's a very active area of research. Nonetheless, the effect of this variant is small. If you carry the variant on average you would be 1.2 kilogram or about two and a half pounds heavier, than if you don't carry the variant. That's like a big splurge on the weekend for some of us I suppose. It's not much of the variance, it's one percent of the variance. This is a small effect. Why are people spending so much time with this small effect? You can account for a lot of obesity based on this. They are spending a lot of time because it's giving them insights what is really right, a very important yet a hard to treat disorder in developed countries. First of all, It appears to be associated with food intake. If you inherit this, this variant, you eat more than other people, probably because you're not getting satiety feedback, the appropriate feedback. The effect occurs, appears to play out very early in development. That is even before people start eating too much. It appears that the biological mechanism may already be established that begins to emphasize the need to intervene very early in life. That's a very important observation even though it's a small effect. Finally, animal models, rodent models of the FTO variant have been created and those are being used to try to test out interventions for obesity. So yes it's a small effect and yes it took a gigantic sample to identify it, but it's producing a very important program of research. Now, to be honest, I don't have a variant like this for schizophrenia today. Two years from now I hope I do. And I hope I can give and example just like this that shows that for schizophrenia, yes it took a lot to, to identify a variant for which it has a very small effect. But it opened up a whole new area of research telling us something very important about schizophrenia. Thank you. Next time I'm going to speculate a little bit about how behavior and genomic medicine will interact. Thank you.
