Introduction à la génétique du comportement humain

Now that we have a foundation in basic biometric and molecular genetics we can begin to look in depth at genetic research for behavioral phenotypes. This week we will focus on schizophrenia. There are several reasons for this focus. First, genetics research has fundamentally changed the way researchers and mental health professionals think about this devastating illness; schizophrenia illustrates the successes as well as the limitations of the genetic approach to a psychiatric illness. Second, research on schizophrenia exemplifies what genetic researchers are finding with most common mental illnesses. Although, for example, the exact chromosomal locations of risk variants and the specific candidate genes implicated certainly vary from one psychiatric illness to the next, the basic features of the genetic architecture appears to be remarkably similar across multiple psychiatric illnesses, at least at this time. So an understanding of the genetics of schizophrenia will bring with it an understanding of much of psychiatric genetics.

Before discussing the genetics research, however, I think it useful that we all know at least a little about what schizophrenia is. Thus the first two modules in this unit describe the clinical phenotype and some of its basic epidemiology, information that will no doubt be very familiar to those of you with a background in clinical psychology or psychiatry. Twin and adoption studies helped to establish the heritable nature of schizophrenia (Module C) and characterize the nature of environmental influence (Module D). The current frontier in genetics research on schizophrenia is to identify the specific genetic variants that underlie its heritability. Initial attempts at identifying risk alleles using the positional cloning strategy were generally unsuccessful yet provided key insights into the nature of the disorder (Module E). Very recently, important breakthroughs have been achieved through Genome Wide Association Studies (GWAS; Module F) and rare variant analysis (Module G). Although the basic foundation for this course was introduced in Units 1-4 and we strive to minimize our use of jargon, sometimes the technical term is exactly what is needed and we will continue to introduce new terms throughout the remainder of the course. So please make use of the Glossary (linked on the navigation bar). We created it in the hope it would help minimize the impact technical jargon might have on your mastering the lecture material.

If there is an area of psychology that generates more heated debate than behavioral genetics it would be the field of intelligence research. While most of us acknowledge the differences among us in personality and even risk for mental illness, for some of us differences in intelligence seem more difficult to accept. I confess I am not completely sure why this is the case. Maybe it is because of the involvement of early intelligence researchers with the Eugenics Movement. Alternatively, maybe it is because the conclusions reached by some intelligence researchers seem to challenge our long-held beliefs about social equality, especially when those conclusions are biologically grounded. Regardless, intelligence, or as I prefer to call it general cognitive ability (GCA), has been a major focus of behavioral genetic research and we will use it as a prototype of behavioral genetic research on a quantitative psychological trait.As with the previous unit, we will begin with a brief discussion of what psychologists mean by intelligence or GCA. I will not try and review the vast empirical literature on the correlates of GCA; suffice to say that GCA is correlated, not always strongly, with many desirable outcomes including educational attainment, occupational achievement, health, mortality, criminal conviction, etc. Twin and adoption studies of GCA have implicated the importance of both genetic and nonshared as well as shared environmental influences. Behavioral genetic research has helped to identify features of the shared environment that appear to contribute to differences in intelligence, but, unlike with schizophrenia and other mental illnesses, it has been difficult to identify the specific genetic variants that contribute to the heritability of GCA. This unit will end with a discussion of genetic research on intellectual disability, an important application of intelligence research.Just FYI, one thing we will NOT consider in this unit but some of you will wonder about is developmental behavioral genetic research on intelligence. I promise that it will be covered in Unit 7.

I am sure many of you wondered about the impact of age on biometric estimates when we discussed general cognitive ability last week. Indeed some of you asked about this issue on the Forums. You were right to raise the question because this is an important issue in the behavioral genetic literature. Given its importance, I thought it might work best to place the question of age moderation in a larger context, which we do this week. We will begin the week by returning to the distinction between shared and non-shared environmental influences, an important distinction in the behavioral genetic literature. You will see that while shared environmental influences are not important for most behavioral phenotypes, there are a few exceptions (including general cognitive ability). However, in all of these exceptional cases, the magnitude of shared environmental influences decreases with age as the heritability increases.

To understand this developmental pattern, at least from a behavioral genetic perspective, it is helpful to consider mechanisms of gene-environment correlation as well as behavioral genetic perspectives on family socialization. We end this unit with an overview of behavioral genetic research on aging.

It is hard to believe we are already to the 8th and final week of the course. This unit begins with an overall summary of human behavioral genetic research organized around four general findings, or ‘laws’ of behavioral genetic research. We will then consider, I suppose more accurate speculate about, the application of behavioral genetic research in the field of individualized or genomic medicine and the implications of behavioral genetic research for personal responsibility. This week’s lectures will also include an interview with Professor Irving Gottesman, a pioneer in the field who undertook pioneering behavioral genetic research on schizophrenia and personality.