Welcome back. This is module F. It's a supplementary module to our 3rd unit on inheribility. And the title of the module is Multivariate Approaches which is a, a grant sounds extremely dry and statistical although we'll try not to make it dry and statistical. In my motivation for including this as a supplementary module to unit three is really my response to a question I often get after talking about twin studies and behavioral genetics. And that's essentially this is it, now that you've done all these twin studies and you know that everything is heritable. Why do you bother continuing to do twin studies? Now, I happen to be a person who continues to do twin studies. Throughout the remainder of this course, we'll talk about examples for why behavioral geneticists would still continue to do twin studies even though we know most things are heritable. We'll talk about longitudinal studies and the importance of twin studies there. We'll talk about the use of twins to characterize the nature of environmental factors. Twins are actually used quite a bit in epigentic research and we'll talk a little bit about that as well. But in this module what I'd like to do is talk about the use of twins in multi-varied analysis. And in muliti-varied analysis really means using twins to try and understand these associations among multiple phenotypes, or multiple traits. And I'm going to try to illustrate this with a very specific example. I think an interesting example. And the example involves what's called by the psychologists and psychiatrists generalized anxiety disorder and major depressive disorder. Now, these are distinct psychiatric disorders. Generalized anxiety, as the name suggests denotes being worrying, and being agitated in, across multiple situations, so it's generalized. Major depression is being despondent, terribly sad, at, at a level that's impairing. Previous twin studies has shown, not surprisingly given what we've talked about that general anxiety disorder is heritable. And this is the results from a meta-analysis. And I can't remember if I've used the term meta-analysis yet in this course. But meta-analysis just involves combining findings from multiple studies to kind of average them to get a very general result. So this is a meta analysis of twin studies of generalized anxiety disorders and roughly a third of the variance, or individual differences in this disorder, are associated with genetic factors, what we call A, and roughly two-thirds with non-shared environmental factors. Shared environmental factors, recall, we call those C factors, don't appear to contribute to risk for generalized anxiety disorder. A very similar meta-analysis of twin studies actually published a year before the, the previous meta-analysis here on anxiety shows similar results. Individual differences in risk for depression, appear to be roughly 35 to 40%, due to genetic factors A, and the balance being due to non-shared environmental factors, E. So that's not really interesting or is nothing really new for us in this course. We kind of knew that, right? Or it would be something like that. The thing I want to illustrate here is what's sometimes called the co-morbidity problem, and basically it's this, is that people who are depressed are often anxious even though those are phenotypically distinct disorders, they tend to co-occur. So, a fairly high percentage of individuals who meet criteria for depression also meet criteria for being anxious. And conversely a very high percentage of people who are anxious are also depressed. And that's what psychiatrists call co-morbidity. Or another way of putting it, is that generalized anxiety is correlated with major depression. And the problem is to try to figure out why. Why are they correlated? What twin studies have to offer in terms of this question is determining whether or not they're correlated because they have common genetic influences or common environmental influences. And because the shared environment is not relevant based on those previous meta analysis for either general anxiety disorder or major depressive disorder,. When we're talking about correlated environmental factors we're talking about correlated non-shared environmental factors. How might twins help us here? Well consider if we had a large sample of monozygotic twins and we assess whether or not they had generalized anxiety disorder and major depressive disorder. And the question is in this large sample, do we often see pairs of monozygotic twins and recall monozygotic twins have the same genotype. Do we often see pairs of monozygotic twins where one twin has an anxiety disorder and the other twin has depression? If we see that with some frequency, then we imagine that probably we're seeing that co-morbidity across the twin pair due to their common genetics. That there must be genetic factors that lead either to having an anxiety disorder, or have depression. And what we're seeing when we're seeing mz twin pairs where one is anxious and one is depressed, is different manifestations of that common genetic risk. So is there really evidence of this? In fact there's quite a bit of evidence for what's illustrated here, and I'm just going to highlight one study. This is actually a classic study in the field. It was done in the early 1990s by a very prominent geneticist. We'll talk about his work several times in this course. A man named Ken Kendler, who's at Virginia Commonwealth University, in Richmond, Virginia. And what he has is a very large sample of twins, both monozygotic and dizygotic. And what I'm plotting here is the correlation he reported in this large study between anxiety and depression. First of all, the correlation within the same individual, this is the comorbidity phenomena, and indeed there's a, remember correlations vary from 0 to 1, so there's actually a strong correlation within the same individual between whether or not he or she has anxiety and depression, 0.67. If we take two random individuals and try to predict, for example, one individual whether or not they have depression from the other randomly selected individual, whether or not that person has anxiety, there is no correlation there because we're, we're pairing two random individuals, so that correlation is zero. The question is, what happens with the twins? In here, I've plotted that. If I take one monozygotic twin, which is plotted here, and see whether or not he or she has depression, and whether that predicts or is correlated with anxiety in the genetically identical co-twin, we see a correlation of 0.37. Not as high as within individual correlation. But higher then the DZ correlation. So we can take one MZ twin and assess whether or not that twin has depression and we can predict whether or not that individual's co twin has anxiety. Well why might that happen? What Kendler suggests in this paper is that when you look at, and he does this with, this is where the fancy statistical modeling comes in. We're, we're not going to go through the fancy statistical modeling. But he does that in this paper, and if you're interested, you can, you can go look at the paper. He looks at anxiety and depression, and what he concludes is that based upon those data that I gave you in the previous slide, that there must be some common genetic factors that accounts for the correlation between the two. And that's why you're getting this pattern in the MZ co twins. So that the genetic factors, and he concludes in this paper, the genetic factors that underly anxiety and depression are actually largely the same factors. They're highly genetically correlated, anxiety and depression. Well then what makes them different? What he includes based on his analysis of what makes them different is the non shared environment. The reason that this is considered a classic paper, is it, is really one of the first demonstrations that suggest that. What we likely inherit is some common genetic risk or common genetic diathesis for developing, either an anxiety or depression disorder or depressive disorder. Which one we develop is going to depend upon the environment we're exposed to. But whether we're, we're at risk is due to common genetic factor that it's the same, largely the same, for anxiety disorders or depression. And this is something that really can only emerge from twin studies. [SOUND] Now since Kendler published his paper in the early 1990s, there have been quite a few additional twin studies that have built on his early work, and I'm going to just summarize them in the next two slides. What those studies have shown is that, building on his work, what behavioral geneticists have shown is that multiple disorders, multiple anxiety disorders. As well as multiple disorders of mood, like depression or dysthymia. All those disorders appear to share a common genetic diathesis. Those disorders are called internalizing disorders in psychiatry. They refer to the, the experience of psychological distress. And they all are comorbid, and they appear to be comorbid because there's some underlying common genetic diathesis to internalize it. You inherit some level of that common genetic diathesis, it can manifest as any one of these disorders depending upon the environment you're exposed to. Alternatively there's another broad class of psychiatric disorders called externalizing or acting out disorders. Disorders of impulse control. Things like drug abuse or alcohol abuse or anti-social behavior. These also are comorbid with one another, and behavioral genetic, or twin studies, have shown that the comorbidity, the correlations to these, among these disorders appears to be due to a common genetic diathesis or risk for developing an externalizing disorder. We all inherit some level of this, as this theory goes, some level of that risk. Whether or not it manifests as a drug disorder or antisocial personality disorder or criminality or another impulse control disorder is going to depend upon the environment we're reared in. So, in conclusion here, multivariate twin studies, one of the things they've really told us about is why thena types come to be correlated. These studies have been extremely important in trying to work out the nosology of psychiatric disorders and in particular for common psychiatric disorders things like anxiety, depression, drug abuse, alcohol abuse. These multi-varied twin studies have indicated that there appear to be two broad underlying dimensions of risk. One for the internalizing disorders, depression and anxiety disorders and the other for the acting out or externalizing disorders. Drug abuse, alcohol abuse, anti-social personality. Thank you. [SOUND]
