Hi and welcome to Unit 2 office hours. I'm Bridget Carey, the TA for the course and of course we have Professor Matt McGrew here. So we've been getting a lot of great questions on the forum and we're here to address some questions on Unit 2, but before we get into that, how are things going? Did you want to say anything? >> Yeah, I agree with you. I think that the, the forums have been very active, and again just like the first week I really found it very informative. I learn a lot there, and I hope the participants in the course also go there to learn things. One thing I wanted to mention is normally, we record these Office Hours on Monday, and they're posted on Tuesday. But next week, actually, I'm going to be in Denmark. And I know we have a few participants from Denmark. But I'm going to be in Denmark, so we can't do next Monday. We're going to actually record Office Hours on Friday. So please, if you have questions, try to get them in the Office Hour forum as early as possible this week, because we're going to be doing the recording Friday morning. >> Well let's start with the questions for this week, and we've had a few on some of the environmental assumptions that go into twin adoption studies. And one comes from Michael Leiden. And he says, one thing that kept bothering me this week was the fact that we assumed that individuals raised in the same home have 100% similar environment. As the oldest of 5 children and being adopted myself, I feel like that isn't true. So what are your thoughts on this? >> Yeah, I, I, well that's good, that's a good point. That's a very fair point and a good question, and it really gets at I think some of the, for some maybe some of the ambiguity of the way behavioral geneticists define the environment. the, the shared environment is really defined effectively rather than objectively, and let me try to explain what that means. What the shared environment is for a behavioral geneticist, and this week you'll see when we talk about biometry as well, the shared environment is defined in terms of the effect of environmental factors, individuals growing up in the same home share that lead to their behavioral similarity. Now, I know that's a mouthful, but let's take a pair of adopted siblings. They're not genetically related, they grow up in the same home. To the extent they're correlated, they're correlated because of features that they share in their environment. Now, that environment might relate to things that actually happen within the home, like the way they're raised. It might also relate to things in their neighborhood or schools they go to. But the important thing is, is that the way we're defining it is by the effect. In contrast, and this is I think where the confusion may arise, we don't actually define the shared environment objectively in these behavioral genetic models. That is suppose you had a family where the parents divorced, now, the natural thing to think is that divorce is a shared, environmental effect. It may be a shared, environmental effect or it may not be. It is depending upon how it affects the children in the family. If the divorce affects children similarly, then its a shared environment. But divorce is, and this is what Mr. Liddon is getting at, the divorce might be experienced differently by different children in the family. >> Mm-hm. >> Depending upon their age, depending upon their gender, depending upon their personality. And to the extent that this objectively shared event leads to differences, is experienced differently by individuals in the home. That's actually a non-shared environmental effect, rather than a shared environmental effect. So the shared environment is defined effectively, what it is in the environments of people reared together that make them psychologically similar. [NOISE] >> And moving on to a question about non-shared environment. Elizabeth Gassen had a followup question, and she was wondering about your opinion on non-shared environment and kind of the niche picking work. >> Well, okay. Those are different really. The, the non-shared environment and niche picking, which is a term I think she's introducing. >> Mm-hm. >> I don't think I use that term. >> Uh-huh. >> But let's all come back to it in a second. But the non shared environment, again is going to be defined effectively. It is the environmental factors that create differences among individuals, who grew up in the same home. Those could be objectively I am not trying to confuse people [LAUGH] but it could be something like a divorce in the family that affects kids differently but it also corresponds to events outside the home, things that are objectively experienced differently by the 2 members of the twin family. One of the things we'll find in this course as we begin to look at data and this is a general conclusion that emerges from behavioral genetic research is that it appears that the non shared environment is much more important to individual differences in behavior than the shared environment. And that, at least when it was initially reported about 25 years ago, was rather surprising. I think now it's pretty well accepted. So, the non-shared environment is something that we're going to be actually talking a lot about as we go through the remainder of the course especially when we talk about phenotypes like schizophrenia. I think another thing that may be important to point out here, and it did come up in the discussion forums about the non-shared environment, is the way the non-shared environment gets defined. It actually includes the effects due to measurement error. >> Mm-hm. >> The inability to accurately and perfectly measure traits, that they're unstable over time. Niche picking is really a different phenomena. Niche picking refers to the phenomena whereby we select environments. We find niches that we find reinforcing, that complement our skills. And the importance of niche picking, and we began to discuss it in this unit, in unit 2. The importance there is that in, when people choose niches or when they choose environments to experience. They often do that in relation to certain psychological traits or skills, or abilities, or personality characteristic or interests they have and to the extent that those personality characteristics or abilities or interests are genetically influenced, then the environments we experience are in part genetically influenced and that might sound a little bit odd. But in fact, that tends to be generally the case for psychological characteristics that we pick environments in a way that seems to complement our genetically influenced tendencies so that mono-zygotic twins do have more similar environments than di-zygotic twins. But why did they have this? They have those, I think in a large degree, because they, they select those environments to be similar. That's what we were trying to illustrate with the life events example. We'll see other examples of this as we go through the course as well. >> Moving on from here, we also had quite a few questions about the adoption study of drug abuse that was done by [UNKNOWN] and Associates. And so Natalie Baranatev asks she says I wonder how we can distinguish between pure genetics and the possibility that the embryo was influenced by drugs in blood circulation of his or her biological mother. Could we possibly look at, separately on drug abuse in biological fathers and mothers? >> Well okay that's a great question and Natalie, I think you actually answered it. I didn't report it when I gave the drug abuse results in the, in the lecture. But in fact they did look at fathers versus mothers and what they found is that the effect not only existed. The effect here we're talking about is that. If the biological parent had drug abuse, did it increase the risk of drug abuse in the reared away biological offspring? And I just reported it for a parent. But in fact, it's true for both fathers and mothers. And in fact it's actually the, the effect was a little bit stronger for the fathers than for the mothers. So the, the specific answer there, Natalie had herself in, in the sense. She, she identified the way to, to kind of explore it by looking at fathers versus mothers. But I think the question actually raises a somewhat larger issue and that is, certainly one of the limitations of adoption studies is that when we're looking at the resemblance between an adopted individual and his or her birth parents, we tend to interpret that as reflecting genetic mechanisms, but there are environmental factors that they, that that individual may share with his or her birth parents. That's certainly the case with the birth mother, who certainly would influence the uterine environment, but maybe also with the birth father. There's some speculation for example that there are some things that are actually transmitted environmentally via the sperm. the, I think the larger point here to recognize is that those possibilities are hard to completely rule out. >> Hm. And because of that, we need to recognize that anyone of the studies we talk about here, an adoption study, a twin study, a reared apart twin study, a family study, has certain limitations associated with them. But the limitations tend to be different across the different studies. And so in this field what we really try to emphasize is the convergence of findings across studies. So if twin studies have their own limitations, adoption studies have their limitations, but if they both appear to be implicating the same set of factors, we become more confident in that inference. It's a general limitation of research in observational psychology. We're not going to do experiments here. So we try to take advantage of what we can take advantage of. >> And then Lisa Marie Gabriel had a question about the graphs in the Kenler Study. And she said one graph showing the showing the relationship between biological parents with a history of drug abuse and their offspring and the second graph showed the results of having adoptive parents with a history of drug abuse compared to their adoptive children. And so her question is, was the second batch of data pulled from those adopted children that have been birthed by parents with history of drug abuse and then raised by adoptive parents with the same history, or was it by biological parents that did not have the history of drug abuse? >> Okay, so a good question, so, I, I, I didn't fully explain this study. What the part of the graph referred to when its talking about adaptive parents with drug abuse versus adaptive parents not having drug abuse. That part of the graph was all adoptive parents. So, the finding in that study that, is that if you had an adopted parent with drug abuse, the adopted child was more likely to develop drug abuse in his or her lifetime. That is some environmental effect, there's no genetic. If, if, if there were selective placement, that's some sort of matching of the biological background with, with the rearing background, I, I suppose there's a possibility that could reflect a genetic mechanism, but it's not really likely. So that in all likelihood is an environmental factor, something about the environment of growing up in a home with an adopted parent. So it is what statisticians, a technical term here, what statisticians would call a main effect. It's a main effect of the adopted family background. If you have an adopted parent with drug abuse, you're more likely to develop drug abuse than if you don't. The point, the larger point I think Lisa's raising here is an important one. It's one we begin to touch on in this week, week 3 not week 2 and that is, well maybe, having an adoptive parent with drug abuse is a greater risk factor if you have a biological background of drug abuse >> Mm. >> Than if you do not. And in fact, I think that's really insightful, Lisa, that you, you identified that issue. I didn't talk about it in this lecture, but in fact that is what they found in this study. That is, when they looked at adopted children who had a birth parent with drug abuse, those children were more likely to develop drug abuse if they had an adoptive parent. That is, growing up in a home with an adoptive parent was, there was a synergy there. There was what we would technically call an interaction. That it was a greater risk for them to be placed in a home of an adoptive parent with drug abuse than a child that didn't have that birth background of drug abuse. That's a phenomena you're going to begin to hear about it in this week. It's a, it, we already touched on it a little bit, called a gene environment interaction. And it's an example, a term that you might not have heard yet, and it comes up in this week's lecture. But I'll just place it here because it is an important term in Psychopathology research, it's called a diathesis stress model. >> Mm-hm. >> And that is the notion that we inherit some, or individuals inherit some vulnerability to develop the disorder whether or not they develop it, depends upon the environment they're placed in. So this would be an example. I didn't talk about it in Unit 2, we're going to talk about it in Unit 3, and example of this diathesis stress or gene environment. Okay so, moving away from adoption studies, let's talk about twin studies. And Linda Singer says, one of the differences between MZ and DZ twins is that some DZ twin pairs are not the same sex. Are there studies that look at these sex differences? And if so, what are the results? And also, are there any discrepancy between male twin pairs when compared to female twin pairs? And do triplets differ systematically from twins? So its [CROSSTALK]. >> Okay, okay there's a lot of questions there. Let me take te last one first. >> Oh. >> Triplets versus twins. I don't know the answer to that one, one's the easy one, I don't know the answer to that one. >> [LAUGH]. >> I, I suspect that they're probably, is not a lot of research on that triplets are pretty rare. I don't even now how rare. They're pretty rare and I don't, a, actually there might be studies out there, I am not just familiar with them. That systematically have a large sample of triplets that could be compared with twins. So I apologize, I just don't know the answer to that one, Linda. The, it's actually an important point you raised, though about same sex versus unlike sex, DZ twins, right. About half the time DZ twins are same sex, and the other half of the time, they're, they would be male-female pairs and does that matter. In general, what twin researchers do is they, they tend not always, but most studies of twins focus just on the same sex DZ twins because they're concerned that twin similarity might be lower in opposite sex or unlike DZ pairs than in same sex. I'm going to come back to an example on that in a second though, it kind of relates to the other, the second question you're asking here. Male male versus female female pairs. That question we can ask of monozygotic as well as dizygotic twins. I think for most of the traits we're going to talk about in this course, we're going to talk about IQ. We're going to talk about schizophrenia. We're going to talk about personality. I don't know of any very compelling data that would suggest that male twins are more or less similar than female twins. But there are some traits that I do know where those do differ. And it actually relates back to the opposite sex versus the same sex. So to try to answer Linda's question, maybe I will give an example. A particular phenotype that we won't talk about in this course which is major depression. Major depression affects women more frequently than it does men. It turns out, in large scaled twin studies, female twins are more similar for depression than male twins and a term that we're going to talk about in Unit 3 but I'll just again refer to it here, that the inheritability of depression appears to be a little bit higher in males, in females, I'm sorry, a little bit higher in females than it is in males. Also, in general although for personality and intelligence it doesn't seem like same sex dizygotic twins are more similar than opposite sex dizygotic twins. For depression, they do differ. Same sex dizygotic twins are more similar than opposite sex dizygotic twins for depression. >> Mm. Why might that be the case? Well there's clearly 2 possibilities. It could be that if you're the same sex, you're more likely to share environmental factors than if you're the opposite sex. The other possibility that might not be as obvious is that if you're the same sex, you may be sharing genetic effects that you don't share if you're opposite sex. That appears to be the case for depression actually. It appears to be that there are genetic factors that affect your risk for depression if you're a woman but those same genetic factors don't appear to affect your risk for depression if you're a man. And it's the existence of those genetic factors that appear to be specific to women that lead women to have a higher, somewhat higher, it's not a lot higher, but somewhat higher heritability for depression. But also lead same sex twins to be more similar than opposite sex twins because those genetic factors are not going to be operating the same in opposite sex DZ twins. So you'll see a bit more discordance and opposite. >> That's right, for depression. then you, you. But for things like, at least to my knowledge, again researchers tend to focus on same sex DZ twins. But to my knowledge for things like schizophrenia, certainly for things like intelligence IQ you don't see a big opposite sex versus same sex difference in DZ twins. >> Next, we have a question from Beth Wegscheider. And she says, in one lecture, you say that since mental illness does not always appear in both MZ twins, environment must be responsible for the difference. However in previous lectures, you've said there are genetic physical anomaly, anomalies in the MZ twins for example the 2 girls in Texas were drastically different in, different in size. >> Okay, so I might be getting inconsistent. >> Yeah. >> It may be a little bit, I suppose. the, there's a couple aspects of this. There's kind of the specific and then I think maybe a broader issue. The specific thing is that we don't know why MZ twinning occurs. But, there has been observations, accumulating observations, and quite a few over the years and we mention this in Unit 2 of monozygotic twins who are discordant for genetic disorders, they could be single gene Mendelian disorders. And how can that be. Well one explanation of that is that there might actually be some sort of genetic mutation that occurs early in embryo-genesis that actually leads, that, that is the factor that creates the monozygotic twinning event. There's some cellular incompatibility that owes to that genetic mutation. So a genetic difference actually might trigger the monozygotic twinning event. And that might explain these young young, or they're not young girls, but these teenage girls from Texas I guess that are quite different in height. It turns out that for all intents and purposes though, if this exists and it may well exist. I think they're enough data to suggest it might exist, this phenomenon. that, it's so small a portion of the genome that people doing twin studies do not worry about it. That they still, and again you'll see this in Unit 3 when we talk about biometric models, they still assume that monozygotic are 100% genetically identical. So yes, it's probably there but its probably a small part of the genome, and not enough to really disturb the, the, the quantitative genetic models that we're going to talk about in week 3. The larger issue, I think, here is, what does it mean to say, what, what is the non shared environment. Now we might initially think of the non shared environment as the psychological environment, but in fact, again it's defined by its effect. It's whatever produces differences in MZ twins. Those differences might correspond to differences in our social environment in our physical environments, but it might also be differences in our cellular environments. In, if there are mutations that we acquire in our lifetime, changes in the DNA sequence that lead to for example, cancer or other diseases, that in a twin study is an environmental event, even though it affects the DNA. So anything that creates discordance in MZ twins is the non-shared environment. And I think that's legitimate there, in the sense that if you acquire a mutation, you acquired a mutation because of some environmental event. So even though it's changing the DNA sequence, it is environmentally induced. >> To end us for the day we have a question from Victor Malkov. And he asks, is there enough research on these outliers and analyzing the reasons why they're so different? He says they're definitely some, like this last year study on MZ twins, on autism discordance that found some epigenetic differences. Okay. So so I, I think I understand the question. So is there a lot research on discordance in twins and I think probably >> I think that's. >> Monozygotic twins. >> Mm-hm. >> Is that right. Well in, in, and we'll begin to see this when we talk about schizophrenia. Sorry to push these things off into the future, but these are things that we do touch on. But they're for important issues, of course. There's actually a lot of research on discordant MZ twins right now. For any mental disorder that we can talk about, they're all heritable to some degree. But monozygotic twins, as we talked about in Unit 2, are never perfectly concordant. So that discordance has to, to be due to something about differences in their environment. What is it in their environments that produce these differences? So, there have been large scale studies of discordant monozygotic twins for schizophrenia, discordant monozygotic twins for autism and many other mental disorders. I, I think, we'll talk a little bit about this in, with schizophrenia again. I think, we, we are beginning to learn a little bit about the, what are the environmental factors that seem to trigger these mental disorders, using this particular research design. In the case of schizophrenia, anticipating what we'll talk about later, we'll see that these studies of discordant MZ twins have really pointed to early life events, in utero events, that might actually be triggering a liability to developing schizophrenia. The question asked also refers to epigenetics. And there's a lot of discussion about epigenetics on the forums. We'll, we'll get to epigenetics. One reason for an interest in studying discordant monozygotic twins, is to look at epigenetic phenomena. And for those of you who are already familiar with epigenetics now, at this point I think all we need to, to say about it is epigenetics, it refers to things that'd change the way genes are expressed. So monozygotic twins might have the same genes but how those express might differ and there are things in their environment that might change that pattern of expression. There's, I think, phenomenal interest in trying to understand could monozygotic twin discordance for schizophrenia or autism be due to how, not the genes per se because that would be the genetic factor, but how those genes are expressed? Is it epigenetic? the, the question asker refers to a study on autism, but if I'm, I think I'm, I, I know the study he's referring to. It was just published recently in Molecular Psychiatry they find some, they report some findings that suggest that that might be the case. There are also some suggestive findings about gene expression differences in monozygotic twins discordant for schizophrenia, I would characterize, I'm a little bit cautious. I think you know this about me. >> Mm-hm. >> I'm a little bit cautious. I would characterize these as very suggestive at this point in time but not definitive studies. We just, I, I would say we need more data. I think epigenetics is an extremely important phenomena for us to consider. I don't think there's enough out there at this time for us to say with great confidence, that's why MZ twins are discordant for autism and schizophrenia. Other people would be more confident in saying that, but for, at least my disposition being a little bit more cautious, I think there's good suggestive data at this point. I'd like to see more. >> And there does seem to be a lot of promising work coming through epigenetics. So, I'm sure we'll have some more definitive answers coming up here soon. >> Yeah. Yeah. Oh yeah. We'll see. There's going to a lot more over the next 3 or 4 years. >> Well, I think that wraps it up for Unit 2 Office Hours. again, just a reminder. Try to get your questions in for Unit 3. Try to get them in as soon as possible so that we can get a recording on Friday morning. All right, thank you. >> Thank you. [BLANK_AUDIO]
