GE Blok 4.docx

GE Interplay – Study Guide Block 4 Lecture 8: Gene and Enviroment corralations (rGE) Although much remains to be learned about the specific mechanisms involved in the pathways between genes and behavior, we know much more about genes than we do about the environment. Genes are located on chromosomes...

GE Interplay – Study Guide Block 4 Lecture 8: Gene and Enviroment corralations (rGE) Although much remains to be learned about the specific mechanisms involved in the pathways between genes and behavior, we know much more about genes than we do about the environment. Genes are located on chromosomes in the nucleus of cells, their information is stored in the four nucleotide bases of DNA, and they are transcribed and then translated using the triplet code. We don’t yet know where environmental influences are expressed in the brain, how they change in development, and how they cause individual differences in behavior. One thing we know for sure about the environment is that it is important. Gene–environment correlations (rGE) occur when there are genetically influenced differences in exposure to environmental risk factors. Genotype-environment interaction refers to the possibility that individuals of different genotypes may respond differently to environments. Genotype-environment correlation, on the other hand, occurs if different genotypes are selectively exposed to different environments. There are three main types of rGE: passive, active, and evocative. Passive genotype-environment correlation What is it? Passive genotype-environment correlation occurs when children passively inherit from their parents' environments that are correlated with their genetic propensities. Parents pass on their genotype and create the environment. Passive genotype-environment correlation requires interactions between genetically related individuals. Genetic predisposition for educational attainment in the parents also creates a good learning environment in the house. Genetic predisposition for depression in the parents also creates a negative/unstable environment in the house. Genotype-environment correlation can also be negative. For example, a sexually risk-taking man may be more likely to father a child with a woman to whom he is not married, such that his child is raised in a father-absent home. At the same time, genetic propensities for sexual risk-taking are heritable; consequently, being raised in a father-absent home becomes associated with the adolescent child’s genetic propensity for sexual risk-taking. It is difficult to tell whether the environmental conditions of a father-absent home influence sexual behavior. Double Advantage model: genetic predisposition for educational attainment and the parents also create a good learning environment in the house. Methods The first method is limited to detecting the passive type. All three methods can also provide evidence for environmental influence free of genotype-environment correlation. The first method compares correlations between environmental measures and traits in nonadoptive and adoptive families. The correlation between parental environment and the behavior of the child is stronger for biological children in comparison to adopted children. In nonadoptive families, a correlation between a measure of family environment and a behavioral trait of children could be environmental in origin, as is usually assumed. However, genetic factors might also contribute to the correlation. Genetic mediation would occur if genetically influenced traits of parents are correlated with the environmental measure and with the children’s trait. A genetic contribution to the covariation between family environment and children’s traits is implied if the correlation is greater in nonadoptive families than in adoptive families. The genetic contribution reflects passive genotype-environment correlation because children in nonadoptive families passively inherit genes and environment from their parents that are correlated with the trait. This source of genetic influence would contribute equally to environment-outcome correlations in nonadoptive and adoptive families. Increased correlations in nonadoptive families would occur only in the presence of passive genotype-environment correlation. The children-of-twins (COT) method can be used to address similar questions. A pseudo-adoption design that allows for control of the genetic risk of parental variables, such as family conflict and parental substance use, to examine whether measures of the family environment have a direct effect on child outcomes or are mediated genetically. Evocative/reactive genotype-environment correlation What is it? Evocative, or reactive, genotype-environment correlation occurs when individuals, based on their genetic propensities, evoke reactions from other people. People around you shape your environment in response to your own (genetically predisposed) behavior. People around you shape your environment in response to your own (genetically predisposed) behavior. The evocative type can be induced by anyone who reacts to individuals based on their genetic proclivities. For example, an early-maturing girl may experience more parent–child conflict as her parents respond negatively to her physically older appearance. If the same genes also predispose her toward earlier sexual activity, there will be an observed correlation between parent–child conflict and age at first sex not because parent–child conflict precipitates sexual behavior but because they are both manifestations of the same underlying genetic difference. Methods Adopted children with a high genetic risk for psychopathology evoke a different environment than children with a low risk. More in the next section. Active genotype-environment correlation What is it? Active genotype-environment correlation occurs when individuals select, modify, construct, or reconstruct experiences that are correlated with their genetic propensities. Individuals create or select their environment based on their genotype. The active type can involve anybody or anything in the environment. For example, an adolescent with dopaminergic genes predisposing her to sensation seeking may shun traditional religious activities, finding them boring, and may be more likely to forego using condoms during her sexual encounters. This will result in a correlation between low religiosity and sexual risk-taking — but, again, not because of any causal environmental influence. Methods Check if MZ twins are more often in the same environment than DZ twins. Evocative and active genotype-environment correlations are assumed to affect both adopted and nonadopted children. The second method involves correlations between birth parents’ traits and adoptive families’ environment assessing the other two types of genotype- environment correlation. Traits of birth parents can be used as an index of adopted children’s genotype, and can be correlated with any measure of the adopted children’s environment. Finding that birth parents’ traits correlate with the environment of their adopted children suggests that the environmental measure reflects genetically influenced characteristics of the adopted children. Adopted children’s genetic propensities evoke reactions from adoptive parents. Multiple strategies can be combined to yield novel information about how genes and environments work together and also help to illustrate the nuances of environmental influences. We may be able to identify genes associated with environmental measures because these are heritable. A big issue across many fields in Psychology is that they ignore that many “environmental” variables have a genetic influence. They ignore the nature of nurture. Of course, environments per se are not inherited; genetic influence comes into the picture because these environmental measures involve behavior that then shapes the environment. Key definitions: Passive genotype-environment correlation: A correlation between genetic and environmental influences that occurs when children inherit genes with effects that covary with their family’s environment. Evocative genotype-environment correlation: A correlation between genetic and environmental influences that occurs when individuals evoke environmental effects that covary with their genetic propensities. Active genotype-environment correlation: A correlation between genetic and environmental influences that occurs when individuals select or construct environments with effects that covary with their genetic propensities. Children-of-twins design: A study that includes parents who are twins and the children of each twin. Extended children-of-twins design: A study that combines a children-of-twins design and a comparable sample of twins who are children and the twins’ parents. Summary Genotype-environment correlation: our experiences are influenced in part by genetic factors. It can be active, passive, or evocative and several methods are available to assess it. The correlation between an environmental measure and a behavioral trait does not necessarily imply exclusively environmental causation. Genetic research often shows that genetic factors are substantially involved in correlations between environmental measures and behavioral traits. What appears to be an environmental risk might actually reflect genetic factors. Conversely, of course, what appears to be a genetic risk might actually reflect environmental factors. This research does not mean that experience is entirely driven by genes. In families of genetically related individuals, associations between measures of the family environment and children’s developmental outcomes cannot be assumed to be purely environmental in origin. Lecture 9: Gene-environment interaction (GxE) + Missing heritability “The whole is greater than the sum of the parts.” – interaction effect Genotype-environment interaction involves genetic sensitivity, or susceptibility, to environments. The effect of the environment on a phenotype depends on genotype or, conversely, the effect of the genotype on a phenotype depends on the environment. In GxE interactions, genetically different individuals will have different experiences (i.e., pay attention to, absorb, or respond differently) to the same environmental stimulation. B – only an effect on the enviroment C – indipendent effect, no interactiong between them For example, a musically talented teenager who frequently listens to a rap song might have her musical ability sharpened if she attends to the song’s complexity and the depth of the lyrics. In contrast, a child who is musically impaired might exhibit no sharpening of musical ability when listening to the exact same song because she ignores all cognitively and artistically engaging aspects of the song, focusing instead only on the profanities. Genes and environments can interact to affect the phenotype beyond the independent prediction of genes and environments. Diathesis-stress model (figure d) – Individuals that are especially sensitive to the effects of stressful environments → vulnerability genes Vantage sensitivity – Individuals gain more than others from a good environment because of being more sensitive Differential Susceptibility Framework (the most realistic, as far as we know) –Individuals are sensitive to both negative as well as positive influences→ plasticity genes GxE is really hard to detect! Because most study designs required to directly test. GE interaction are unethical to do in humans. And the ethical ones require huge sample sizes and extensive collection of environmental data. Animal and plant models Both genotype and environment can be manipulated. Despite the power of animal model research to manipulate genotype and environment, there is surprisingly little systematic research on genotype-environment interaction. Study on mouse twins separeted when young Study design Enrriched enviroment Testing the influence of gene, enviorment, and the interaction In a mixed model ther was an indipendent effect of genes and enviroment. Surprisingly there wa no interaction effect. Slides 19-26 The best explanation: The Transactional Model of cognitive development – “Children select and evoke experiences in line with their genetic predispositions. As these experiences, in turn, stimulate their cognitive development, early genetic influences on cognition will become amplified Genes impact cognition You choose enviorments you can learn from. You know what to pay attention to Snowball effect – addictive genetic affect/influence – multiple genes coming together for a joint bigget effect Human research Children are born with all of their genes. As they grow, they experience more and more environments. Some studies found heritability is different in distinct socioeconomic levels: high heritability among rich families and much lower heritability in poor families. What could be behind these differences in heritability? Gene-Environment interactions (GxE)! (and perhaps some active rGE as well). The Scarr-Rowe hypothesis – a supportive environment (high SES) enlarges the difference between individuals with higher and lower genetic predispositions. Caution, though! In research, these results about SES are still contested and unclear! The explanation for the GxE could be very different. Compensatory Advantage Hypothesis (CAH) – high SES compensates for genetic challenges. Or there might be no GxE (when looking at genetic markers and polygenic scores). What if the (social) environment does not allow individuals to select freely? Or if the environment does not give individuals many opportunities for “talents” to thrive? The variance explained by the genetic effects would be smaller. These come with the discussion on value and ethics that we will get back to! Missing heritability There is a big and obvious gap between the heritability estimates from twin/family studies and the heritability captured by polygenic signals from GWAS (which is a lot smaller). The gap between the blue and orange bars is called missing heritability. Candidate genes The era of candidate genes was the dark ages of genetics. Individual genes rarely replicate. Even those that do, usually account for less than 0.1% of the variance. Candidate gene studies are not trustworthy because most could not be replicated. There were some big studies that were thought to be true, but in the end, they were not. To date, many studies have reported genotype-environment interactions, most focusing on the genes involved in these first studies. However, caution is needed when considering the findings of studies examining candidate gene-by-environment interactions. Genome-wide approaches, which utilize DNA variation across the genome, have also begun to be applied in the search for genome-wide gene-by-environment interaction. Finding genes is difficult and it might even be hopeless. Because of the definition and subtypes. There are multiple genes with small effects. Interactions and correlations with the environment. Endophenotypes An endophenotype (also known as intermediate phenotype) is a quantitative biological trait that is reliable in reflecting the function of a discrete biological system and is reasonably heritable, and as such is more closely related to the root cause of the disease than the broad clinical phenotype. Key definitions Genotype-environment interaction – genetic sensitivity or susceptibility to environments. Genotype-environment interaction is usually limited to statistical Interactions, such as genetic effects that differ in different environments. The most common use of the twin method in studying genotype-environment interaction involves testing whether heritability differs in different environments (not only with twins). Diathesis-stress – a type of genotype-environment interaction in which individuals at genetic risk for a disorder (diathesis) are especially sensitive to the effects of risky (stress) environments. Candidate gene-by-environment interaction –genotype-environment interaction in which an association between a particular (candidate) gene and a phenotype differs in different environments. Genome-wide gene-by-environment interaction – a method for searching for genotype- environment interaction that assesses DNA variation throughout the genome. Vantage sensitivity: Individuals gaining more than others from a good environment because of being more sensitive. Differential susceptibility framework (the most real, as far as we know) – individuals are sensitive to both negative as well as positive influences → plasticity genes. Summary Two main foci: Genotype-environment interaction: Animal studies, in which both genotype and environment can be controlled, have yielded examples in which environmental effects on behavior differ as a function of genotype. Examples of genotype-environment interaction for human behavior have also been found in adoption and twin studies and in molecular genetic studies using functional polymorphisms in candidate genes. What is clear from this research is that genes and environment operate together to influence behavior through genotype-environment correlations and interactions. Understanding how nature and nurture correlate and interact will be greatly facilitated as more genes are identified that are associated with behavior and with experience.