Behavioral Genetics in Psychology - Summary PDF

BEHAVIOR GENETICS IN PSYCHOLOGY Historical perspective and Mendelian laws History of behavioral genetics Theory of Preformationism (Leeuwenhoek/Hartsoeker): we all come from miniature versions of ourselves. Sperm contain complete preformed individuals called homunculus. - They believed the homunculus carries homunculus etc. - The mother doesn’t bring anything, she only the homunculus so that the homunculus can grow - It doesn’t make sense because all the children should resemble their father and that isn’t the case Karl von Linne (Linneaus): Published a comprehensive taxonomy of all known living organisms, classifying them into distinct species based on the belief that species were unchanging. Law of use and disuse: the view that Lamarck started, that species passed on traits that acquired during their life to their offspring. Galton: he studied the inheritance of mental characteristics. He was the founder of median, percentiles and correlation. Thereby, he also introduced to use twins to study the roles of nature and nurture. - ‘Nature prevails enormously over nurture’. This was the start of the nature-nurture debate. - Eminent status was more likely to appear in close relatives, with the likelihood of eminence decreasing as the degree of relationship became more remote. Darwin’s provisional hypothesis of pangenesis: every cell in produces gemmules. They carry information about specific traits and accumulate (verzamelen) in the reproductive organs. Darwin believed that all gemmules were passed on to the offspring. Environment could affect gemmules. - It is incorrect but a first attempt to explain heredity. - Blending inheritance: the traits of mother and father blend o If everything blends, than over time everybody looks the same and is variation gone. Everybody looks average. This theory affects the theory of natural selection. - Variation was the most difficult component to explain Mendel’s first law Pedigrees describes family trees. Amino acids are the building blocks of proteins The law of segregation: there are two elements of heredity for each trait, a dominate (S) and a recessive (s) elements. Offspring receive one of these two elements. These elements separate, or segregate during reproduction. These elements are now called alleles. Each individual inherits two alleles for each gene. - Ended the theories of blended inheritance of Darwin Punnett square: a diagram used to predict the genotypes of a cross or breeding experiment. Useful to determine the probability of an offspring having a particular genotype Genotype: individual’s combination of alleles Phenotype: observed traits Huntington disease Brain disorder causing deterioration of brain cells that leads to severe incapacitation and eventual death - Symptoms: uncontrollable movements, abnormal balance when walking, slurred speech, thinking difficulties and personality changes - No cure or effective treatment It is caused by a dominant allele. Affected individuals have one dominant allele (H) and one recessive allele (h). So the risk of getting HD is 50%, there needs to be one parent with HD in order to get the disease. This lethal (dodelijke) condition exist in the population, because the lethal effect is not expressed until after the reproductive years. The gene of HD is on chromosome 4, showed by DNA markers. Most people decide not to take the test to reveal whether they have the HD gene or not. Phenylketonuria BEHAVIOR GENETICS IN PSYCHOLOGY Metabolic disorder that prevents normal metabolization of phenylalanine which is present in protein rich foods. Damage occurs to the nervous system leading to mental retardation. Prevention is done by diet. It is a recessive disease, in order to get this disease you need two recessive genes from your parents. You are a carrier if you carry one recessive allele of a recessive disease. The risk of getting PKU is 25% if both of your parents are carriers. 50% are becoming carriers. The chance of getting PKU, if one of your parents has PKU and the other is a carrier, is 50%. Recessive traits are more seen if the parents are genetic related. Hardy-Weinberg equilibrium: the frequencies of alleles and genotypes do not change across generations unless forces such as natural selection or migration change them. - Homozygous dominant genotype: p x p = p2 - Homozygous recessive genotype: q x q = q2 - Heterozygous genotype: p2 + 2pq + q2 = (p + q)2 Population genetics: researchers that study the forces that change allelic frequencies On chromosome 12. Mendel’s second law Law of independent assortment: the inheritance of one gene is not affected by the inheritance of another gene. - Linkage: if two genes lie relative close to each other on the same chromosome. These two traits are not inherited independently. Only two types were found, dominant for both A and B and recessive for both A and B. The reason is that during recombination there is a lower chance these genes will be separated. - Recombination: the process by which chromosomes exchange genetic material during meiosis, resulting in a new combination of alleles. This exchange happens through crossing over. - Exceptions: for genes on different and for genes that are far apart of the same chromosome. X- linked inheritance - Exceptation: genes in close proximity on the same chromosome. Traits will be passed down depended. These genes are separated Genes are carried on chromosomes. They are located at places called loci on chromosomes. This picture illustrates the recombination of three loci (A, B, C) on a single chromosome. During meiosis each chromosome duplicates to form sister chromatids (b). These sisters chromatids may carry over (c). This happens one time during meiosis for each chromosome. Chromatids bcan break and rejoin (d). Each of the chromatids will be transmitted to a different gamete (e). Crossover occur less between A and C loci. Centimorgan: the distance between two loci that describes the likelihood of recombination between two genes or markers on a chromosome. One centimorgan corresponds to 1% chance that crossover will occur between two loci. Linkage analysis: the technique that use information about violations (inbreuk) of independent assortment (classificatie) to identify the chromosomal location of a gene. Beyond Mendal’s law Morbidity risk estimate (lifetime expectancy): chance of being affected during an entire lifetime BEHAVIOR GENETICS IN PSYCHOLOGY - First-degree relative: parent/sibling - Second-degree relative: grandparent/aunt/uncle - If several family members are affected, the chance is higher. Quantitative dimensions: vary in degree across a spectrum rather than existing as discrete categories. - Many psychological, physical and biochemical traits Polygenetic trait: characteristic influenced by multiple genes, rather than a single gene. Most traits are not recessive or dominant, this is called additive. You add a bit to the phenotype. All traits have some additive effect. Additive genetic variance refers to the independent effects of alleles or loci that ‘add up’, in contrast to nonaddictive effects of dominance within a locus, and epistasis across loci in which the effects of alleles or loci interact. Mendelian traits: - On or a few genes - Big effects from each gene - Causation is deterministic - We know the biological mechanisms, not for all, but for the most of it - Environment or experiences don’t have a affect - Examples: Huntington’s disease, hemophilia, cystic fibrosis Complex traits: - Influenced by many genes, each effect has a tiny effect - Causation is probabilistic - We have little idea of the mechanisms - Environment plays a major role and interact with genes - Examples: Alzheimer, schizophrenia, depression Quantitative genetics: multiple-gene effects lead to quantitative traits (continuum) First-degree relatives (proband) are one step removed, two-degree relatives two steps etc. Liability-threshold model: explain the inheritance of complex traits that appear as qualitative (present or not) traits, such as mental health disorders - Liability: the underlying, continuous risk factor for developing a disorder. It is the result of genetic and environmental factors. Color blindness Two types - Difficult distinguish between red and green (most common) o A condition caused by a lack of certain color-absorbing pigments in the retina of the eye o If the mother is color blind and the father not, all the sons are color blind but the daughters not. When the father is color blind and the mother not, the offspring are seldom affected. But half of the grandsons of the daughter are color blind. This is known as skip-a-generation phenomenon o It is caused by a recessive allele on the X-chromosome. Fathers passed their recessive allele on the X-chromosome on to their daughter. If the mother isn’t color blind, she will pass on her ‘healthy’ X-chromosome. So the daughter is a carrier. If she get a son it is a 50% chance she will pass on her recessive X-chromosome, so the son will be color blind, because he get the Y-chromosome of his father. - Difficult distinguish between blue and yellow DNA mutation frequently occur in cells other than those that produces eggs/sperm and are not passed on to the next generation. This is also the cause of many cancers. Estimating genetics and environmental influences with family designs Heritability Statistical significance: the reliability of the effect. It depends on the size of the effect and the sample. BEHAVIOR GENETICS IN PSYCHOLOGY Effect size: how much genetics contributes to a trait, the extent to which individual differences for the trait in the population can be accounted for by genetic difference among individuals. It refers to differences in the entire population, not for certain individuals. - Genetic effect sizes are one of the largest effects, accounting for as much as half the variance Heritability: the proportion of phenotypic variance that can be accounted for by genetic differences among individuals. - For example, if heritability for IQ is 50%, half of the differences in IQ scores are due to genetic factors, and the rest due to environmental factors - Can be estimated from the correlations for relatives - For first-degree genetic relatives, if the heritability is 100%, their correlation would be 0.50 Concordance: index of risk getting a disorder/disease. The likelihood that two people (twins) have the disorder Model fitting: tests the significane of the fit between a model of genetic and environmental relatedness against the observerd data using structural equation modeling (SEM). Which is a statistical method for testing a conceptual or theoretical model. In behavioral genetics this method is used to estimate heritability and environmentality based on the similarity and differences among family members. It is difficult to identify the specific genes responsible for heritability SNP heritability: how much of the variation in a trait across a population can be attributed to differences in SNPs among individuals. The genetic similarity is used to predict phenotypic similarity for individuals. SNPs are small genetic variations in DNA where a single nucleotide differs from one person to another. Interpreting heritability The causes of average difference between groups are not necessarily related to the causes of individual differences within groups. Heritability doesn’t say ‘what should be’ What are some potential issues with the adoption design? - Not representative, it is only a part of society, because rich parents don’t let their kids adopted. - Prenatal environment, 9 months in mother’s womb - Selective placement, it is not random, parents are selectively selected. How do we measure twins similarities and differences? With correlation What are issues with twin studies? - Equal environments assumption: environmentally causes similarity is roughly the same for both types of twins reared in the same family. o If the assumption were violated because identical twins experience more similar environments than fraternal twins, this violation would inflate estimates of genetic influence Environmentality Shared environmental (C) influences refer to all nongenetic influences that make family members similar to one another. Like neighborhood, parental education, family factors etc. It will only be shared environmental influences only if they result in greater similarity among individuals living in the same household. And only the amount that is not itself a function of genetic relatedness. Nonshared environment/Unique environmental effects (E) are all nongenetic influences that are independent (or uncorrelated) for family members, including error of measurement. Like different family experiences or different experiences outside the house. BEHAVIOR GENETICS IN PSYCHOLOGY Calculating ACE What can a high correlation among MZ twins tell us? That it is genetic What can a low correlation among DZ twins tell us? That is genetic - If it goes down by half it is genetic, if it is high its environment You can only say something about this, if you combine these questions. Alone it means nothing Multivariate analysis: estimates the extent to which the same genetic and environmental factors affect different traits - The essence of this analysis is the analysis of cross-covariance in relatives, which refers to the covariance between trait X in one twin and a different trait, trait Y, in the co-twin - The genetic correlation: estimates the extent to which genetic deviations that affect X literally correlate with genetic deviations that affect Y o Independent of heritability - Bivariate heritability: estimates the contribution of genetic influences to the phenotypic correlation between the two traits Univariate analysis: estimate the relative contributions of genetic and environmental factors to the variance of a trait The genetic correlation: estimates the extent to which genetic devia tions that affect X literally correlate with genetic deviations that affect Y - Independent of heritability We know that genes are located on chromosomes in the nucleus of cells, how their information is stored in the four nucleotide bases of DNA, and how they are transcribed and then translated using the triplet code. The biological basis of heredity DNA structure Nucleotide: a base paired with a sugar and phosphate group - Phosphate group: a molecule that helps form the backbone of the DNA or RNA strand - Sugar group: DNA contains deoxyribose and RNA contains ribose - Nitrogenous bases: A, T, C, G Polynucleotide: very long molecule of repeat units called nucleotides, they form a chain - DNA and RNA are both polynucleotide DNA: the molecule that is responsible for heredity. Located in the nucleus Contains of two strings held apart by pairs of four bases: adenine, thymine, guanine and cytosine - Adenine – thymine - Guanine – cytosine o The pairing is important for replicating and to direct synthesis of proteins o Hydrogen bonding, this creates the double helix shape BEHAVIOR GENETICS IN PSYCHOLOGY - Back bone always consist sugar and phosphate molecules - Strands coil around each other to form double helix of DNA Codon: a sequence of three bases in DNA or RNA that codes for a specific amino acid or the end of a transcribed sequence or a signal in the protein synthesis process - For example, AUG, GGA, UAA - There are 64 possible codons Genes: portions of DNA, which can code for proteins The different amino acids There are 20 amino acids, each with a basic structure that includes: - A carbon atom (C). - An amino group (NH₂). - A carboxyl group (COOH). - A variable R group (side chain) that can differ among amino acids. The R group can be classified into different categories: - Nonpolar: R groups that do not interact well with water (hydrophobic). - Polar: R groups that can interact with water (hydrophilic). - Negatively Charged: R groups that carry a negative charge (acidic). - Positively Charged: R groups that carry a positive charge (basic). - The variations in the R group affect how amino acids interact with each other. This interaction influences protein folding: the specific folding of a protein is crucial because the structure determines the function of that protein Functions of DNA - Replicating: The double helix unzips, the bases separate. Leading to two strands, both attracting the right bases, so that there are two new helix’s formed. This is the essence of life. - Synthesis of proteins: DNA encodes the various sequences of the 20 amino acids making up the thousands of specific proteins o DNA (transcription)  RNA (translation) protein Transcription: DNA transcribes in message, it occurs in the nucleus 1. To get DNA out of the cell, RNA is needed 2. Helicase (enzyme) unwinds and separates the two strands of the DNA double helix (zipper being unzipped) 3. RNA connect complementary bases, which leads to one string of mRNA - There is one exception, the A now binds with U instead of T 4. mRNA gets out of the nucleus and binds on a ribosome. The ribosomes are the factories that make proteins. Ribosomes are made of rRNA Translation: the genetic information in mRNA is read and converted into a sequence of amino acids, forming a protein 1. In the cytoplasm there are free tRNA. They carry an amino acids (building block for protein) on them. tRNA brings amino acids together to make proteins. 2. mRNA decides which tRNA is needed for the protein that is making. tRNA is looking for complementary bases, if they find one, they bind. The tRNA is the anticodon. 3. tRNA leaves, but leaves the amino acid behind. 4. Amino acids are held together by a peptide bond 5. The stop codons signal the end of protein synthesis - UAA, UAG, UGA After translation proteins can undergo posttranslational modification (changes made in proteins), which further affect their functions. The key enzymes and processes involved in DNA replication: DNA replication is the process by which a cell makes a copy of its DNA before cell division. This ensures that each new cell receives an exact copy of the genetic material. BEHAVIOR GENETICS IN PSYCHOLOGY 1. Helicase: an enzyme that unwinds and separates the two strands of the DNA double helix, creating two single strands that will be copied à like a zipper being unzipped - Binding proteins attach to the unwound single strand of DNA to stabilize them 2. 5' to 3' Direction: When new DNA is made, it grows from the 5' end to the 3' end. You can only add new parts to the end that’s 3'. - 3' to 5' Reading Direction: The existing DNA is read backwards from the 3' end to the 5' end to know what new pieces to add. 3. Primase: primase is an enzyme that synthesizes a short segment of RNA called an RNA primer. this primer is like a starting point for DNA polymerase to begin building a new DNA strand. - Without this prima, DNA polymerase wouldn’t know where to start 4. DNA polymerase III: this enzyme extends the RNA primer by adding DNA nucleotides to create a new DNA strand. It uses the template strand (the original strand being copied) to add complementary nucleotides - If the template has an adenine (A), it will add a thymine (T) to the new strand 5. DNA polymerase I: after DNA Polymerase III has synthesized the new DNA strand, DNA Polymerase I comes in to remove the RNA primer and replace it with DNA nucleotides. This ensures that the entire new strand is made of DNA. 6. Ligase: connects any fragments of DNA together RNA processing After RNA is made from DNA (transcription), it goes through some important steps to become fully functional: 1. End-modification: the heads and tails are capped (5’ end) and a poly A tail is added to the end (3’ end). 2. Splicing: non-coding regions (introns) are removed from the RNA molecule. The coding regions (exons) are kept and joined together 3. Cutting events: the RNA molecule may be cut into smaller pieces 4. Chemical modification: additional chemical groups may be added to the RNA molecule. The genetic code: the set of rules that dictates how sequences of codons in DNA (or RNA) are translated into proteins. It defines which amino acids corresponds to each codon. It is universal among individuals Genome: the complete set of genetic material (DNA) in an organism. It includes all of the genes as well as the non-coding regions of DNA that play roles in regulation and other cellular functions. Contains all the information necessary for an organism to grow, develop and reproduce. - 3 billion DNA base pairs organized into 46 chromosomes - The genome is located in the nucleus of cells - Carries instructions for building and maintaining an organism, including production of proteins and regulation of gene expression. - There is no single human genome, we all have different genomes Genes are part of the genome, and the genome is made up of DNA BEHAVIOR GENETICS IN PSYCHOLOGY Alternative splicing: exons (coding regions) are joined to gather to make mRNA. Exons can be combined in different ways to produce different mRNA molecules from the same primary RNA transcript The twentieth century is the century of the gene. Human microbiome: the genomes of the microbes that live in and on our bodies Epigenome: chemical marks on our DNA that regulate gene expression Chromosomes Sex chromosomes: one pair of our chromosomes that determine whether you’re a boy or a girl Autosomes: all the other chromosomes Chromosomes contain genes Gene mapping: locating on chromosomes using ‘bands’. - Bands: identify chromosomes, dark and light bands on chromosomes are visible under a microscope after staining. These bands are used as ‘landmarks’ to identify gene locations’ - For example, the gene for Huntington disease is at 4p16 (short arm of chromosome 4 at a particular band, number 6 in region 1) Centromere: a region of the chromosome without genes. It is where the chromosome is attached to its new copy when cells reproduce p: short arm q: long arm below the centromere Types of cell division 1. Mitosis: cell division in somatic cells. Each chromosome duplicates and divides to produce two identical cells - somatic cells are diploid (46 chromosomes) 2. Meiosis: cell division that occurs during gamete formation and results in halving the number of chromosome, so that each gamete contains only one member of each chromosome pair, thus 23 chromosomes - Germ cells (gametes): egg and sperm cells. They are haploid, meaning they have half the chromosomes (23), so that when they combine during fertilization, they create a cell with a full set of chromosomes (46). Chromosomal abnormalities - Nondisjunction: uneven split of the pairs of chromosomes during meiosis o For example, down syndrome (nondisjunction of chromosome 21) o Most fertilized eggs have nondisjunction, but this will normally lead to spontaneous abortion - Chromosomal abnormalities mostly lead to cognitive inability - Missing or having an extra chromosome is lethal, except from the sex chromosomes. o In females one of the two X are inactived, most of the genes are not transcribed. This is also the case with an extra sex chromosome, so it is not lethal. Thus when you have an extra X chromosome (XXX or XXY) only one X chromosome is active. Microarrays: Omics A field of study in biology that looks at entire sets of molecules within a cell or organism, rather than focusing on one molecule or gene at a time. - (genome, proteome, transcriptome) Each omics level (e.g., genome, proteome, transcriptome) represents a layer in the process of how genetic information is translated into physical traits or functions. These omics levels do not work in isolation; they constantly interact with each other and with environmental factors. - The omics approach allows scientists to study biological systems as interconnected networks rather than isolated parts. In summary, an omics level perspective looks at the whole system rather than individual parts, allowing for a deeper understanding of how genes, proteins, and environmental factors interact to produce complex biological functions. BEHAVIOR GENETICS IN PSYCHOLOGY Cell types - Eukaryotes: Organisms with cells that contain membrane- bound compartments, including a nucleus and other organelles. This group includes animals, plants, fungi, and protists. - Prokaryotes: Organisms (like bacteria) with cells that lack membrane-bound compartments. They have a simpler structure and do not have a nucleus or other membrane- enclosed organelles. Identifying genes Recombination: shuffling of the genes Quantitative trait locus (GTL): regions of the genome that contain one or more genes influencing continuous traits. They play a central role in understanding how complex traits are inherited and can aid in breeding programs and disease research - Quantitative traits: traits that show continuous variation in a population, like height, weight, blood pressure etc. - Qualitative traits: distinct categories, you have it or don’t have it - Controlled by multiple genes that interact with each other and with the environment - The regions can contain multiple genes - To identify QTLs it usually involves creating genetic maps - The expression of a QTL could differ in different climates or under different nutrient conditions BEHAVIOR GENETICS IN PSYCHOLOGY Three ways to identify genes 1. Linkage: a technique that detects linkage between DNA markers and traits, used to map genes to chromosomes 2. Candidate gene approach: looking at associations between genetic variation within pre- specified genes of interest and phenotypes or disease states 3. Genome-wide association study (GWAS): scan the entire genome for common genetic variation. Goal is to identify single nucleotide polymorphisms (SNPs) that are associated with phenotypic traits Mutations A mutation that loss a single base is more damaging than a mutation that causes a replacement (substitution). Deleting mutations can cause frameshift, this changes the way te sequence of codons is read, which often results in a different protein. A substitution mutation only affects one amino acids of it hasn’t an effect. Expanded triplet repeat: specific triplets are repeated more than normal, leading to disrupted normal gene functions, which can lead to hereditary disorders like Huntington disease. The number of repeats determines whether or not a disorder develops and how severe it may become. Repeated sequences: very short segments of DNA repeated a few times or up to a few dozen times - Used as DNA markers Genetic anticipation: symptoms appear at early ages and with greater severity in successive generations - Why this happens: As triplet repeats expand with each generation, the number of repeats increases, which can make the disorder appear sooner and often more severe in the next generation. Premutation: individuals with higher repeats, but not high enough the cause a disorder. But they can pass it on to their offspring, which may expand to full mutation and maybe leading to a disease. They are carriers. Detecting polymorphisms DNA polymorphisms: a locus with two or more alleles. Variations in the DNA sequence that occur at specific loci within the genome, and they play a significant role in genetic diversity, disease association, and individual traits. Polymorphisms can be used to track inherited traits, locate disease- causing genes, and understand human genetic variation. 1. Microsatellite markers (STRs): sections of DNA where a short sequence of 2-6 base pairs is repeated multiple times in a row, often have many alleles that are inherited. They vary greatly between individuals 2. Single nucleotide polymorphisms (SNPs): a change in a single nucleotide at a specific position in the DNA sequence - 2 possibles alleles on one location. This means you can have either a A or G for example. - Most common type of genetic variation in the human genome - Changes in the first codon - Bi-allelic: can have 4 states - - Hoe kan een t tegenover een t komen? - Nonsynonymous: change in an amino acid sequence. Which affect the protein’s shape, function or stability. There are functional - Synonymous: no change in amino acid, because multiple codons can code for the same amino acid. The protein itself doesn’t change, but there is a small difference in the DNA. But they still can have an effect on how genes work. It can change the rate at which mRNA is translated into proteins - Recombinational hotspots: blocks (Haplotype blocks) of SNPs that are highly correlated o Groups of SNPs that are inherited together due to their physical proximity on a chromosome are known as haplotype blocks. These blocks can be used to track genetic variations across populations or to map disease-causing genes. BEHAVIOR GENETICS IN PSYCHOLOGY - Haploid genotype (haplotype): A haplotype refers to the specific combination of alleles or genetic markers on a single chromosome inherited from one parent. It can represent the genetic sequence on one chromosome of a pair (as opposed to the diploid genotype, which involves both chromosomes). Copy number variants (CNVs): duplication or deletion of long stretches of DNA, often encompassing protein-coding genes as well as non-coding genes. Frequently used more broadly to refer to all structural variation in DNA, including insertions and deletions Polymerase chain reaction (PCR): a molecular biology technique used to amplify (make millions of copies of) a specific region of DNA. It is one of the most commonly used techniques in genetic research, diagnostics, and forensic science. - Detection of all DNA markers, because PCR makes millions of copies of a small piece of DNA - Primers: 20-base DNA sequence that marks the starting point for DNA replication. Primers on either side of a polymorphism mark the boundaries of a DNA sequence that is to be amplified by polymerase chain reaction (PCR). Are unique in the genome and identify the precise location of the polymorphism - Polymerase: begins the copying of DNA Whole-genome sequencing: detecting every single DNA polymorphism by sequencing each individual’s entire genome Human behavior Two major strategies for identifying genes - Linkage analysis: a technique that detects that linkage between DNA markers and traits, used to map genes to chromosomes. Linkage can be identified by using pedigrees o Well suited for genes with large effect sizes. They cannot detect for small effect sizes - Allelic association: an association between allelic frequencies and a phenotype o Direct association: DNA marker on functional gene, so that the allelic association can be detected o Indirect association/linkage disequilibrium: DNA marker very close to the functional gene  Linkage of 1.0 alleles of the DNA markers are perfectly correlated  0.0 means no correlation Linkage telescope  association microscope Linkage is systematic but not powerful for detecting genes of small effect size. Candidate gene allelic association is powerful but not systematic. It can be made more systematic by using dense map of markers Complex disorders - The affected sib-pair linkage design: based on allele sharing o 25% no sharing o 50% sharing one allele o 25% sharing both alleles SNP microarrays: tools used to detect and analyze thousands of SNPs across an entire genome simultaneously. Helping with study genetic variation, associations with disease and population genetics - Microarrays: a glass slide the size of a postage stamp dotted with short DNA sequences called probes. Each probe is designed to bind a specific SNP or DNA sequence o Detecting SNPs - Restriction enzymes: proteins cut DNA at specific sequences o SNPs can create or remove restriction enzyme BEHAVIOR GENETICS IN PSYCHOLOGY - Whole-genome amplification: creating multiple copies of an entire genome from a small DNA sample. o Useful if there is only a small DNA sample available or when there needs to be multiple analyses need to be conducted on the same DNA Genomewide association study (GWAS): A study that assesses the association between individual differences in a quantitative character and DNA variation throughout the genome. - GWAS is very useful for discovering new disease biology and improving clinical prediction models. However, GWAS has some limitations/issues; minority populations underrepresented within European samples and Asian and African samples are quite rare. - How does it work: a large number of individuals are recruited for the study. Divided in to two groups: affected group (have the condition) and the control group. DNA is collected from all participant via blood/saliva samples. This is analyzed for SNPs. The frequency of the SNPs are compared between the affected and the control group. The idea is to found out which SNPs are more common in the affected individuals than in the control individuals - Limitations o The missing heritability problem: gap between genomewide identified associations and heritability. Such as twin and family designs o It’s difficult to identift a single genetic cause, because many traits and disease are affect by multiple genes and environmental factors o May not be generalizable to other populations How should we investigate genetic effects? We can change the genotype of the fertilized egg cell or we rerun the entire lifecycle. This is also possible for a group. Continuous phenotype: on a spectrum, like height. You can be between 130 and 210 cm. Why should we try and do gene finding? - Learn about disease biology - Predict disease based on the genome - If we know, for each SNP, its effect on disease. And we measure SNPs in patients, we can predict the risk of disease - Use genetic to improve epidemiology Biological annotation - What is the lesson here (1)? o Hypothesis free scan of the entire genome implicates gene, we don’t have hypothesis linked to traits o Follow up of the gene (not previously deemed interesting) reveals a disease mechanism  this is why GWAS are good for  which variance/SNPs/genes can causes your trait/phenotype o The gene can be a possible therapeutic target, maybe you can design a drug for Nature, nurture and human behavior Quantitative genetics: estimates the extent to which observed differences among individuals are due to genetic differences of any sort and to environmental differences of any sort without specifying what the specific genes or environmental factors are. - Provides the best available evidence for the importance of environmental influences Twin studies You can tell if twins are identical or fraternal by DNA markers. If they differ in DNA markers, they must be fraternal Equal environments assumption: similarity cause by environment is roughly the same for both types of twins reared in the same family Identical twins experience greater prenatal differences than fraternal twins. They show greater birth weight differences. This is may due to the greater prenatal competition, because they share the same chorion. BEHAVIOR GENETICS IN PSYCHOLOGY Language develops slower in twins, perform less well on test of verbal ability and IQ in comparison to singleton children. Adaption design is more powerful by adding the family design (genetic-plus-environmental) Measuring heritability - Sequences of SNPs, we only need the variance - Correlations - Looking at all the SNPs - Manhattan plot o X: all different chromosomes (SNPs) o Y: significance o The higher ones are associated with the trait The meaning of heritability - If there are no differences there is nothing to do at heritability. Everyone is the same - Heritability is about the differences between people. Always in references with the population. o Hight heritability is not equal to genetic determinism - Heritability is about differences based on the average o So heritability is relative to a particular context - Heritability describes what is and not what could be o Genetic influences we find in research explain the cause of the differences in a trait at that moment in time and in that environment (and in a certain population). Of course, the same is true for environmental influences o Even a heritability of 100% doesn’t mean that the environment is powerless ti change the trait. Future interventions could change/trait the trait - Heritability can differ between populations. It does not have to be an explanation of differences between populations/groups - Heritability can change over time - What explain differences in trait, that is wat heritability explains Heredity: the transmission of genetic information from parents to offspring. It describes the way genes are inherited and is the process by which traits or characteristics are passed down through generations. - The genes themselves are involved in determining a characteristic - Genes are controlling it, but it doesn’t mean that there is heritability for it, because if there are no differences than there is no heritability - About what the genes are causing Laws of behavior genetics 1. All human behavioral traits are heritable 2. The effect of being raised in the same family is smaller than the effect of genes - A is bigger than C 3. A substantial portion of the variation in complex human behavioral traits is not accounted for by the effects of genes of families - E is large The interplay between genes and environment Discoveries about nature-nurture 1. Nonshared environmental influences are surprisingly large and important in explaining individual differences 2. Many environmental measures widely used in the behavioral sciences show genetic influence - People create their own experiences - Nature of nurture = genotype-environment correlation. It refers to experiences that are correlated with genetic propensities BEHAVIOR GENETICS IN PSYCHOLOGY 3. The effects of the environment can depend on genetics and that the effects of genetics can depend on the environment - Genotype-environment interaction Beyond heritability Heritabilities are seldom higher than 50 percent. Thus environmental factors are also important Quantitative genetic research goes beyond heritability 1. Multivariate genetic analysis investigates the origins of the covariance between behaviors, instead of estimating influences on the variance of one behavior at a time 2. Investigating the origins of continuity and change in development 3. Behavioral genetics considers the interface between nature and nurture. Genotype-environment correlation = the nature of nurture What seem to environmental effects van reflect genetic influence because these experiences are influenced by genetic differences among individuals Is the genetic control of exposure to the environment Passive and evocative are there at the same time Passive genotype-environment correlation: passively inherit from their parents family environments that are correlated with their genetic propensities. - Parents create an environment for children through their behavior - Double advantage model: Parents are double evolved in the life of their children (genotype and environment) o This always happens o We don’t acknowledge this - Double disadvantage model: for example, parents pass the genes on for sensitivity for mental health disorder, and because they suffer from their own mental health disorder they are less available, more negative etc. - Strong during childhood and parents are not active creating your environment when you’re an adult - For example, musically gifted parents provide their children with both genes and environment to develop musical ability - Testing with an adoption study. The non-adoptive family should be stronger if it is a passive rGE - Testing with children of twin design (COT) o High genetic risk and environmental risk  double disadvantage model Evocative/reactive genotype-environment correlation: individuals, on the basis of their genetic propensities, evoke reactions from other people - Due to your genotype, you evoke a reaction from the environment. Most of the time you cannot do anything do about it - Children evoke a parent style of the parents. This is in any reaction with a human being. Someone else’s genotype evokes a behavior in you. - Musically talented children picked out at school and given special opportunities - Active genotype-environment correlation: individuals select, modify, construct or reconstruct experiences that are correlated with their genetic propensities - Based on your genotype, you select an environment - Selecting musical friends - Testing with any twin studies BEHAVIOR GENETICS IN PSYCHOLOGY If the correlation of mz twins is higher than the correlation of dz twins, than there is a genetic component SES: based on income and educational level (dependent on your genotype) - Driven by differences between people Three methods to investigate the contribution of genetic factors to the correlation between an environmental measure and a behavioral trait 1. Detecting the passive type: comparing correlations between environmental measures and traits in nonadoptive and adoptive families 2. Detecting evocative and active type: comparing correlations between birth parents traits and adoptive families environment 3. Detecting all three types: multivariate genetic analysis of the correlation between an environmental measure and a trait We may be able to identify genes associated with environmental measures because these are heritable 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. It is that the effect of the environment on a phenotype depends on genotype or that the effect of the environment on a phenotype depends on the environment. If you get the same environmental influence it has a different effect on everyone, because all of us have a different genotype. For example, if you discuss the lecture at home, everyone will discuss something else, because we are all different. Explain the interaction: Diathesis-stress model: individuals at genetic risk for psychopathology are especially sensitive to the effects of stressful environments. Vantage sensitivity: gaining more than other from a good environment because of being more sensitive Differential susceptibility framework: individuals sensitive to both negative as well as positive influences  plasticity genes Candidate gene- by- environment interaction: genotype-environment interaction in which an association between a particular (candidate) gene and a phenotype differs in different environments. Genomewide gene- by- environment interaction: A method for searching for genotype- environment interaction that assesses DNA variation throughout the genome. Pathways between genes and behavior Heritability means that DNA variation creates behavioral variation, and we need to find these DNA sequences to understand the mechanisms by which genes affect behavior. Functional genomics: The study of how genes work by tracing pathways among genes, brain, and behavior. It usually implies a bottom- up approach that begins with molecules in a cell, in contrast to behavioral genomics. BEHAVIOR GENETICS IN PSYCHOLOGY Behavioral genomics: The study of how genes throughout the genome function at the behavioral level of analysis. In contrast to functional genomics, behavioral genomics is a top- down approach to understanding how genes work in terms of the behavior of the whole organism. Explanations for MZ discordance - Environment - Epigenetic differences - De novo mutations - Chance Gene expression and the role of epigenetics Epigenome: epigenetic events throughout the genome that influence gene expression - Sits on top or outside of the genome - Tells your cells to switch on or off - Imprinting: changing gene expression from on cell to its daughter cells and in some case from one generation to another Gene expression: changes in the rate of transcription of mRNA are used to control the rate at which genes produce proteins - DNA methylation: attachment of a methylgroup to DNA building blocks. This result in turning a gene off or silence and there will be no more producing protein from that gene. o Cannot attach to every nucleotide only to a C o CpG island (occur in the promotor of genes): a C next to a G o Promoter usually represses gene expression o Can differ between individuals, due to 3 main causes  Environment (chemical exposure, diet, prenatal development)  Genetic (SNPs that influence methylation level/gene expression level)  Stochastic (random) - Histone modification: o Histones: proteins wrapped around DNA - Non-coding RNA is important in regulating gene expression of protein coding DNA o Introns: DNA sequences that are transcribed into RNA but are spliced out before the RNA leaves the nucleus.  regulating expression o Exons: the DNA sequence that are translated into amino acid sequences (proteins) o microRNA: binding on RNA and than regulating the expression. A class of non- coding RNA involving 21 to 25 nucleotides that can degrade or silence gene expression by binding with messenger RNA. - Genes can only function if they are expressed - Epigenetic mark: transmitted during mitosis to daughter cells RNA is tissue-, age- and state-specific. This is why RNA can respond to environmental changes by regulating the transcription and translation of protein-coding DNA. This is the basis for gene expression. Epigenetics: focus on gene expression that do not alter DNA sequence and can be passed on to its daughter cell. Literally it means ‘above genetics’. How DNA interacts with multiple molecules within cells, which can activate or deactivate genes. - Epigenetic landscape: on top they have the potential to become different cell types. Because of gravidity the fall down and fall in a route that the decide what kind of cell they are becoming. When a cell became a brain cell, it cannot become another cell anymore. - Role of epigenetic mechanisms o Tissue-specific gene expression o Development-specific gene expression BEHAVIOR GENETICS IN PSYCHOLOGY o Adjusting to environment - Epigenome mapping projects: creating extensive maps of different cell types in the human body, at different stages of development o Which genes are transcribed? o Which regions are methylated? o Which regions are accessible? - Epigenetics prove that not everything is in our genes and that the environment can make changes The transcriptome: gene expression throughout the genome Transcriptome: RNA transcribed from all genomic DNA Housekeeping genes: expressed at a steady rate in most of our cells Gene expression profiling: Using microarrays to assess the expression of all genes in the genome simultaneously. - Can create an atlas of localized patterns of gene expression throughout the brain Expression QTL (eQTL): when treating gene expression as a phenotype, QTLs can be identified that account for genetic influence on individual differences in gene expression. The proteome: proteins coded throughout the transcriptome Proteome: all the proteins translated from RNA - There are more proteins than genes - After amino acid sequences are translated from messenger RNA, they undergo modifications, called posttranslational modifications, that change their structure and thus change their function. - Proteins do not work in isolation. Their function is affected by interactions with other proteins - Electrophoresis: A method used to separate DNA fragments or proteins by size. when an electrical charge is applied to DNA fragments or proteins in a gel, smaller fragments travel farther. o Identifying proteome by using gels in an electrical field Endophenotypes: an inside of intermediate phenotype that is causally related to overt behavior Neurome: effects of the genome throughout the brain OMICS: the collective characterization &quantification of pools of biological molecules that translate into the structure, function, and dynamics of an organism - Proteome - Neurone - Epigenome GWAS: which variants in the DNA sequence are associated with a trait or disease - Which letters differs between people EWAS (epigenome-wide association studies): which epigenetic mark in cells… 1. Collecting DNA samples in large groups 2. Measuring DNA methylation in each person 3. For each location: test if DNA methylation differs between two groups of people Discordant (differ on particular feature) monozygotic twin design - Comparing DNA methylation patterns of phenotypically-discordant monozygotic twins - Rules out many other explanations or differences between cases and control (confounders) - They have same sex etc. Central dogma of molecular biology - Transcription  splicing  translation  posttranslational modification Each cells contains the same genome, even if they don’t have the same function SNPs - More than 90% are located in non-coding DNA - These SNPs influence gene expression rather than protein structure/function BEHAVIOR GENETICS IN PSYCHOLOGY - The effect is often in a specific tissue What is the underlying biological pathway of early life adversity that is linked to behavioral problems and mental health conditions in childhood and adulthood? - Early life exposure can have a long lasting effect Substance use disorder Drug addiction is a disease - Addiction: Chronic, relapsing brain disease that is characterised by compulsive drug seeking and use, despite harmful consequences. It is considered a brain disease because drugs change the brain. Drug use is a choice, drug addiction not. Alcohol dependence Two syndromes: - Alcohol abuse disorder: focused on the problems in daily life - Alcohol dependency: focused on withdrawal It is heterogeneous Heritability: - Genetic factors play a major role in the family aggregation of alcohol dependence - Shared environment is related to alcohol use in adolescence and young adulthood but not for later alcohol abuse. - Genetic risk for alcohol use is greater in more permissive environments (unmarried, nonreligious, greater availability etc.) - Heritability can change with age, can be different in different environments, can differ for DSM components Nicotine dependence Strong support for the genetic role in smoking Results of twin and adoption studies of alcohol- related behaviors suggest moderate heritability and little evidence for shared environmental influences. Single liability model: Initiation to smoke and dependency are part of the same dimension. Independent liability model: initiation dimension and dependency dimension are independent of each other. Combined model(CM): Initiation and dependency are two different dimensions that are not independent. Most evidence for smoking Conclusion: There is low heritability of initiation (the first cigarette). Heritability of nicotine dependency is much higher. Additionally, the environment often plays a large role in initiation, and genes determine the development. Parental monitoring moderates the importance of genetics and environmental influences on adolescent smoking. Monitoring made A and E influence less present, and C more present. Parental monitoring: The extent to which parents know what their children are doing and discuss this with them. Cannabis 24%of the adult population (18-65 yrs) used cannabis at least once in their life. 7.5% used cannabis in 2018. Cannabis abuse is 0,6% in men and 0,2% in women, and cannabis dependence is 0,4% in menand0,1%in women. BEHAVIOR GENETICS IN PSYCHOLOGY Heritability: No gene-policy interaction (no gene-environment interaction). No effect of drug policy on heritability of cannabis initiation. Overlap for drugs - Phenotypic overlap: Overlap between using one drug and another drug (see table). - Genetic overlap: They found that genes for illegal drugs overlap and genes for legal drugs overlap. There is around 60% genetic overlap for alcohol, nicotine and cannabis addiction. Shared environmental influence plays the largest role for initiation of smoking. Finding the genes that are involved Two pathways: 1. Pharmacodynamic pathway: pathway related to neurotransmission. What happens in the brain? For example, neurotransmitters that make you relaxed. 2. Pharmacokinetic pathway: pathway that contains the metabolism (breaking down alcohol) Psychopharmacogenetics: genetic effects on behavioral responses to drugs Pharmacogenomics: examine genetic efforts on a genomewide basis, focus on genetic differences in positive and negative effects of drugs in order to individualize and optimize drug therapy. Gene set analysis: To conclude: - Heritability is less important in drug initiation than later use. - Effects for the shared environment mainly in initial stages of drug use. - Many genes are involved in the path from initiation to problem use and these genes do only partly overlap across phases. - Heritability for illegal drugs is also high and similar genes may play a role in different addictions. - G x E is present but needs more study. - Knowledge about genes may guide interventions. - In the future epigenetic will tell us more about the path from gene to addiction. - GWA studies are beginning to yield some consistent findings for alcohol and smoking. But less findings for other drugs, such as cannabis, methamphetamine, and heroin. Cognitive abilities and education General cognitive ability (g)  also called IQ - Understand complex ideas, adapt effectively to the environment, learn form experience, engage in various forms of reasoning, overcome obstacles by taking thought - Very reliable, valid, stable in adulthood - It is a strong predictor for many social, educational, and occupational outcomes - Explains 40% of the variance among tests, most of the variance of specific test is thus independent of g. there is thus more cognitive abilities than g - 50% of the variance explained by A. Thus there is some heritability - Cognitive abilities have share environmental influence o 1/3 of the variance is explained by C - Heritability increased during development - Common environment decreases during development - Unique environment increases a little bit A: genetic C: common environment  anything that makes twins more similar BEHAVIOR GENETICS IN PSYCHOLOGY - C is not the same for parent and offspring, because they don’t really share the same experiences as how siblings do with each other E: own unique environment  anything that makes twins less similar Neurocognitive measure of cognitive abilities Certain neurocognitive traits / parts are heritable and correlated with g: - Executive function and working memory are highly heritable and correlated with g. - Reaction time is heritable and correlated with g. - Brain volume and volume of certain brain areas correlates moderately (0.4) with g. - Thinning of the cerebral cortex during adolescence is highly heritable. - Structural measures of connectivity is highly heritable and correlated with g. - High cognitive ability is associated with less brain activation (more efficient) School achievement We see a lot of genetic overlap between domains of school achievement and cognitive abilities g. The difference between achievement and ability is that achievement implies effort, while ability is based on genetic influence. High intelligent people tend to do reasonably well in both math and language, while the less intelligent tend to struggle with both. Only a small minority of the students excel in one subject but fail miserably at the other (this is rare). This shows the correlation between language and math. From this we can conclude that the same genes affect diverse cognitive and learning abilities (generalist genes). Generalist genes hypothesis: Most genes associated with common learning disabilities (such as developmental language disorder (SLI), dyslexia, and dyscalculia) are generalists: Meaning that - Genes that affect common learning disabilities are largely the same genes responsible for normal variation in learning abilities. - Genes that affect one learning disability are also likely to affect other learning disabilities We think that we are better in one than the other because we compare with our peer group and not with the average person. Genetic findings about cognitive abilities 1. Heritability increased during development - How is it possible that it increases during development? Due to genetic amplification, a process where genetic nudges early in development are magnified as time goes by, with the same genetic factors creating larger and larger phenotypic effects o The only exception is school achievement, this is more heritable in the early school years and remains high throughout schooling 2. Assortative mating is substantial - Assortative mating is the phenotypic correlation between spouses. It is greater for cognitive abilities than for other traits such as personality. This has important implications for the genetic architecture of cognitive abilities 3. The same gens affect divers cognitive and learning abilities - Relates to the generalist gene hypothesis already explained above. General cognitive disability (intellectual disability) Impairments in cognitive abilities that impact adaptive functioning in skills/domains such as personal care and job responsibilities. - Mild general cognitive disability: IQ 50 to 70. - Moderate general cognitive disability: IQ 35 to 50. - Severe general cognitive disability: IQ 20 to 35. - Profound general cognitive disability: IQ below 20. General Cognitive Disability: Quantitative Genetics BEHAVIOR GENETICS IN PSYCHOLOGY Siblings of children with mild cognitive disability tend to have lower IQ scores (than average), as would be expected by an inheritable trait. However, moderate and severe cognitive disability may largely be due to non-heritable factors meaning that there is no familial resemblance. General Cognitive Disability: Single-Gene Disorders Phenylketonuria (PKU): Mutations in the PAH gene that produces the enzyme phenylalanine hydroxylase lead to an enzyme that does not efficiently break down phenylalanine. Phenylalanine comes from protein rich food. - IQ < 50 - Solution: diet low in phenylalanine Fragile X syndrome (FRX): - Second mot common cause of cognitive disability - Men: IQ declines after childhood - More in men than in women - Happens through permutation. The risk that a permutation will expand to a full mutation increase over four generation from 5 to 50 percent o Thefullmutation causes hypermethylation → shuts down transcription of the FMR1 gene → no FMRPprotein → diverse problems. Rett syndrome (RS) - Males doesn’t survive - The first year there is normal development - Problems with language, coordination and repetitive movements General cognitive disability: chromosomal abnormalities Cytogenetics: A branch of genetics concerned with the study of the structure and function of the cell, especially the chromosomes. Down syndrome: caused by a trisomy (extra chromosome) of chromosome 21 leading to overexpression of several hundreds of genes. - Most important cause of general cognitive disability - Symptoms: Increased neck tissue, muscle weakness, speckled iris of the eye, open mouth, protruding tongue, cognitive disability (IQ 55) and short stature. - Additionally, ⅔ have hearing deficits and ⅓ have heart defects → average lifespan of 50 years. Those who reach the age of 45 suffer from dementia. - Down syndrome is an example of an exception to Mendel’s laws because it does not run in families. - Occurs more often in women giving birth later in life due to nondisjunction. o Nondisjunction: The failure of one or more pairs of homologous chromosomes or sister chromatids to separate normally during nuclear division. It activates immature eggs that have been dormant for decades. Sex chromosome abnormalities Extra X chromosomes also cause cognitive disabilities, although the effect is highly variable because extra X chromosomes are largely inactivated. Small chromosomal deletions These structural variations in chromosomes are called copy number variants (CNVs). Most CNVs arise de novo during meiosis when a DNA segment is deleted on one chromosome and duplicated on the corresponding member of the chromosome pair. The figure summarizes the average effect on IQ Specific cognitive disabilities Specific cognitive disabilities: Disabilities in relation to school-related difficulties such as reading, communication, and mathematics. - Dyslexia: reading slow and often with poor comprehension - Communication disorder: consists of four types; language, speech, stuttering, social communication - Dyscalculia: poor performance on mathematics BEHAVIOR GENETICS IN PSYCHOLOGY The results of these common disorders suggest that disability is quantitatively, not qualitatively, different from normal variation in ability. This implies that the heritability of the disability is caused by many genes of small effect, a conclusion that will be repeated in the following chapters about other common disorders and complex traits Assortative Mating Assortative mating: A nonrandom mating pattern where individuals similar to each other mate with one another more frequently than what we would expect under a random mating pattern. This leads to non-zero spousal correlation: For a specific trait, the couple is more correlated than two random people. For example, height, IQ (0.4), years of education (0.6), political view and religion. Assortative mating can be caused by: - Assortment: Initial selection of a similar mate. o Genetic assortative mating: assortative mating based on similar genetics. - Convergence: Couples become more similar over time. Assortative mating has important implications for the genetic architecture of cognitive abilities because it increases the offspring’s additive genetic variance: The independent effects of alleles or loci that add up. Because offspring inherit only one of each of the parents’ pairs of alleles, offspring do not resemble their parents for nonadditive interactions. Result → The genotype of parents are more similar than random → offspring (and their genotypes) are more similar to their parents → siblings (and their genotypes) are more similar to each other. This affects the estimation of heritability for 3 models. If assortative mating were not taken into account: - Parent-offspring study (birth parent and adopted apart offspring): You overestimate the heritability because you overestimate the correlation between the birth parents and the child - Twin model: Assortative mating increases DZ correlation but not MZ correlation. Meaning that A is underestimated and C is overestimated. - GWAS: Assortative mating increases the genetic variance in a population. → overestimation of SNP heritability. GWAS of cognition and educational attainment There are 3 ways to identify genes: - Linkage: Problem is that it is not really appropriate for quantitative traits. - Candidate gene approach: Problem is that it does not replicate. - Genome-wide association study (GWAS): most successful one. But it needs huge sample size. GWAS of Educational attainment They looked at the number of years of schooling as a measure of educational attainment. It was easy to obtain data and therefore easy to obtain a big sample size (N= 1.1 million) → 1271 independent SNP that are significantly associated with educational attainment. The SNP heritability was 0.11, the twin heritability was 0.4, the heritability in between is called missing heritability. May be due to too small sample size, or they only looked at common genetic variance instead of all genetic variance. GWAS of cognitive ability They looked at cognitive ability. They found 242 independent SNP with SNP heritability 0.19 and twin heritability of g 0.5. N=265867. You can also use GWAS to look at where the genes associated with cognitive ability are expressed in the body. Most of these genes were in the brain tissue, however there were also many in the hormonal tissue. Adult mental disorders: MDD, schizophrenia, eating disorders etc. Schizophrenia A chronic and severe mental disorder that affects how a person thinks, feels, and behaves. BEHAVIOR GENETICS IN PSYCHOLOGY - Positive signs: Hallucinations, delusions, thought disorders, movement disorders. - Negative signs: Relational deficits (social withdrawal), affective deficits (difficulty showing emotions), avolition (lack of motivation), communicative deficits (lacking in speech) or difficulty in functioning normally. Risk for schizophrenia is based on the number of risk carrying genes. The more of these genes, the larger the chance of developing schizophrenia. The GWAS was a success, they found 108 schizophrenia-associated genetic loci. There were many genes with small effects. However, one gene stood out: component 4 (C4). This gene is involved in synaptic pruning, leading to less neuron connections than with a different variant of that gene. Depression Major depressive disorder: Includes depressed mood, loss of interest in usual activities, disturbance of appetite and sleep, loss of energy, and thoughts of death or suicide. Slow onset over weeks or even months. Each episode typically lasts several months and ends gradually. Lifetime risk is 17% in the U.S. With the depression DSM-5 Diagnostic Criteria you need 5 of the 8 symptoms for a period longer than 2 weeks. Genes: The GWAS of genes related to depression is less successful than with schizophrenia. GWAS analyses identify 44 risk variants and refine the genetic architecture of major depression. - They found that the FHIT gene is related to depression, but also involved in the circadian clock. - Genes that were identified by this study were related to brain patterns and gene expression in the brain. The FHIT gene is also related to these processes in the brain. - The FHIT gene is also related to day time sleepiness (symptom of depression) Bipolar disorder Bipolar disorder (manic-depressive illness): A disorder in which the mood of the affected individual alternates between the depressive pole and the mania pole. Lifetime prevalence 4%. But, much higher heritability estimate than for unipolar; 85% (substantial heritability). Mania: involves euphoria, inflated self-esteem, sleeplessness, talkativeness, racing thoughts, distractibility, hyperactivity, and reckless behavior. Begins and ends suddenly, lasting from days to several months. Bipolar I disorder: Characterized by extremely elevated moods during manic episodes and, frequently, depressive episodes as well. Focus is on the danger of manic episodes. Bipolar II disorder: Characterized by alternating periods of extremely depressed and hypomania (mildly elevated moods). Focus is on the depression episodes. Bipolar disorder can be seen as a more severe form of depression Generalized anxiety disorder Anxiety, experienced as excessive, uncontrollable worry about a variety of topics in the absence of stimuli or in a disproportionate manner to their real risk. - Risk increases when family members also have the disorder (familial). - Meta-analysis: Heritability of 31.6% (around the same as for depression) - Same predisposing genes in men and women, but these genes are more often expressed in women. - A small influence of the common familial environment in females. Patients often have multiple disorders together (comorbidity). - In depression patients, 67% has current and 75% has lifetime comorbid anxiety disorder diagnosis. - In anxiety patients, 63% current and 81% lifetime depressive disorder diagnosis. - The correlation of genes having an influence on major depression, and genes having an influence on anxiety disorder is 1.0. This means that there is a 100% overlap. - There is also overlap of unique environments, but this is much less. - The expression is different and this must come from the unique environment BEHAVIOR GENETICS IN PSYCHOLOGY Post-traumatic stress disorder (PTSD) A disorder that develops in some people who have experienced a shocking, scary, or dangerous event. - Not every traumatized person develops PTSD - Not everyone with PTSD has been through a dangerous event To be diagnosed with PTSD, an adult must have all of the following for at least 1 month: - At least one re-experiencing symptom. - At least one avoidance symptom. - At least two arousal and reactivity symptoms. - At least two cognition and mood symptoms. Heritability Yes, PTSD is heritable. However, heritability estimates depend strongly on the sample. They found SNPs in 22 genes related to PTSD, including genes related to dopamine and serotonin and HPA-axis (cortisol) functioning. Heritability of PTSD is related to genes and DNA methylation Eating disorders Anorexia nervosa (28-58% heritability): See themselves as overweight, even when dangerously underweight. Extreme dieting, avoidance of food, vomiting, using lataxives and exercising excessively. Lifetime prevalence 0,6%. 2. Bulimia nervosa (54-83% heritability): Binge eating followed by vomiting. Lifetime prevalence 1,0%. - Family members of a patient with an eating disorder have a greater chance of developing an eating disorder (3-12% vs. 0-4%) - For anorexia this is 11.3 x higher, for bulimia 4.4-9.6 x higher - Both occur mostly in adolescent girls and young women. No shared environmental influence. The genetic and unique environmental risk factors for AN and BN are partly the same. - Anorexia and OCD often co-occur. Genetic cross-correlation is high (r=.49), combination is heritable (21%), and correlates with other disorders and measurements. Binge eating disorder (70% heritability): Binge eating and feelings of lack of control and distress. Lifetime prevalence 2,8%. A distinction can be made between binge eating (BE) and night eating (NE). Divorced parents increase the risk of eating disorders Personality disorder Personality: distinctive and relatively stable pattern of behavior, thoughts, motives, and emotions that characterizes an individual Personality traits: relatively enduring individual differences in behavior that are stable across time and across situations - Most are heritable (30-50%) - Shared environment plays almost no role in personality, nonshared environment does (60%), but shared environment may be important at the extremes of personality o Personality questionnaires are filled out by the person itself, thus the tests are biased Big five personality traits 1. Openness: creative, imaginative, intellectual - A: 45%, E:55% 2. Conscientiousness: organized, neat, orderly, practical, prompt - A: 38%, E: 62% 3. Extraversion: talkative, assertive, forward, outspoken - A: 45%, E: 55% 4. Agreeableness: sympathetic, kind, warm, understanding, sincere - A: 35%, E:65% 5. Neuroticism: moody, anxious, insecure - A: 47%, E: 53% BEHAVIOR GENETICS IN PSYCHOLOGY The big five traits are all fairly stable. However, there are some changes over the life span, until 25 years. Neuroticism decline during the life span and conscientiousness increases. Why is our personality so stable? It is because how we structured society. After college we live a ‘stable’ live. This limits the amount of changes in your life. As a kid you go to different schools, meet a lot of new people, you’re exposed to different perspectives etc. The big reason for stable personality is genes. Unique life experiences guide the stabilization of personality across the life span. So it is not your genetics and brain maturation Genes for personality - Genes are difficult to find due to the huge amount of factors in a personality trait. - Heritability explained by common SNPs is low (10%). o The missing heritability - Success story: Polygenic score was predictive of neuroticism score. - Some of the genes found for neuroticism are also involved in depression and schizophrenia. - Many studies have shown associations with specific genes but ultimately there will be many genes involved. They found; - Heritability o Heritability of personality is not visible at birth. o Heritability in childhood is higher than in adulthood. So it decreases with age o The stability in personality across age is due to genes. Genes environment interplay For women there is a heritable component for all 3 types expect uncontrollable events. This is not the case for men. That does not mean that men have less control over events, it might mean that this control is less explained by genes and more by environment. The gene effect in women was not directly related to the event (getting married or divorced). It was related to genes for personality traits: Genes → Personality → Life events - Controllable events (getting married or divorced). - Uncontrollable events (serious illness in child or death of spouse). - Desirable events (major improvement in financial status or buying a house). - Undesirable events (major deterioration in financial status or death of child). Another study looked at the quality of marriage with 326 Swedish female twin pairs and their partners. They found that heritability influences satisfaction, conflict and warmth of their marriages - Satisfaction has 35% heritability. 35% of the variation in satisfaction is due to genes. - Warmth has 21% heritability. - Satisfaction has 26% heritability for report by husband. - Optimism and aggression explain 30% of the variance in satisfaction of marriage. - 50% of the genes associated with optimism and aggression overlap with the genes found for satisfaction of marriage. Change in heritability: Having gone through a divorce in combination with gender may determine the relative influence of genes and environment on attitude such that; - A: Heritability (genes) play a larger role in the attitude towards divorce if you did not have a divorce, than if you did have a divorce. BEHAVIOR GENETICS IN PSYCHOLOGY - E: For both men and women, the attitude towards divorce is strongly influenced by the unique environment. - C: For men the common environment is especially a strong determinant of the attitude towards divorce after they had a divorce The power of parents - The shared environment of the home (C) generally has little influence on personality traits. The way your parents raised you doesn’t have to do that much with your personality. - Few parents have a rearing style that is consistent - Even when parents try to be consistent, there may be little relation between what they do and how their children turn out. EnWAS: A GWAS but then with a lot of different environments instead of different genomes. - A lot less different environments than genomes. In a GWAS you use millions of genomes, but it is harder to find a million different environments. Sexual preference Genes play a role in sexual preference, but they do not determine everything - Many genes with small effects play a role - No single dimension in hetero vs. homo preference (not yes or no matter) - Sociocultural context also plays a role in explaining individual differences - The misconception that ‘the more someone is attracted to the same-sex the less they are attracted to the opposite-sex’. o It is not one dimensional - Because there is no genetic correlation, there needs to be two dimensions o You can be highly attracted to women but also to men. You can be both a 10 Personality disorder Psychiatric disorders are at the extremes of quantitative personality traits. Personality disorders are at the border between personality and psychopathology. They are part of the genetic continuum of psychopathology. Personality disorder prevalence: 4,4- 13,5% of the adult population has at least one personality disorder. The personality disorders are organized in clusters: 1. Cluster A personality disorders: Characterized by odd, eccentric thinking or behavior. For example, schizotypal personality disorder. - Schizotypal personality disorder: Someone who has great difficulty in establishing and maintaining close relationships with others, are unusually superstitious or preoccupied with paranormal phenomena that are outside the norms of their subculture. - Heritability +/- 40%, but varying degree - Genetic overlap with schizophrenia 2. Cluster B personality disorders: Characterized by dramatic, overly emotional or unpredictable thinking or behavior. For example antisocial personality disorder. - Antisocial Personality Disorder: Pattern of behavior in which individuals consistently disregard and violate the rights of others around them. - More often in men than in women - Related to increased risk of drug use and criminality - Ferguson: 56% of variance explained by A, 11% by C and 31% by E. 3. Cluster C personality disorders: Characterized by anxious, fearful thinking or behavior. For example Obsessive-compulsive personality disorder. BEHAVIOR GENETICS IN PSYCHOLOGY - Obsessive-compulsive personality disorder: Preoccupation with orderliness, perfectionism, and mental and interpersonal control, at the expense of flexibility, openness, and efficiency - Heritable but degree not yet well established - Genetic overlap with OCD Antisocial Personality Disorder and criminal behavior Individuals with ASP often had parents who were arrested. The chances that ASP individuals were arrested was higher if their parents also were arrested. → gene-environment interaction. Increased risk of ASP in men when there is maltreatment during childhood in combination with low activity of MAOA gene. (not found in women). From adolescence to adulthood, genetic influence increases and shared environmental influence decreases for symptoms of antisocial personality disorder, including juvenile delinquency and adult criminal behavior Neurodevelopmental disorders: autism, ADHD, etc. Autism - Traditionally, the diagnoses of autism contained impairments in three areas; social interactions, communication, and interests (repetitive behavior) before 3 years of age. - Asperger syndrome: Impaired in the social and interests domains but normal communication development before 3 years of age Autism spectrum disorder (ASD) - Symptoms of ASD are typically evident before the age of 3 years. - The first noticeable delays are often related to speech and language. - The global prevalence of ASD is around 1%. - The ratio in boys versus girls is 4:1. Problem is that the rating is the same (and more based on boys), maybe if this is fixed the difference in ratio disappears. - A third to half of children with an ASD diagnosis have an intellectual disability (IQ < 70). - ASD is diagnosed along the entire range of cognitive ability (see figure). Two decades ago, autism was thought to be an environmental disorder. - Refrigerator mother theory: ‘cold parenting’, - Minimal brain damage leads to autism. - Vaccinations: A paper claimed that one of the vaccinations children receive, leads to autism. Problem with paper, sample size is 12, made-up data, weird conclusion. Took them 12 years to retract this paper (why?). Now, twin studies suggest that it is one of the most heritable disorders. The relative risk in MZ twins was 60%, in DZ twins / siblings it was between 0 and 5%. This shows that it is driven by genes, but not only determined by genes. Additionally, relatives of individuals with autism show increased rates of social deficits, impairments in communication and language, a preference for routines, and difficulty with change. Autism disorder also confirms the rule that disorders are actually the quantitative extreme of a continuum of normal variation. Note: A surprising finding is that the three symptoms (impairments in social, communication and interest) have low genetic correlations. This suggest that, although some children by chance have all three symptoms, the ASD triad of symptoms are genetically different Identifying genes Although the results of linkage studies and candidate gene studies have not yet been successful, there is accumulating evidence that rare variations in chromosomes (e.g., CNVs) play an important role. The lack of success in finding common variants might be because the components of the autistic triad are genetically different. A new GWA study found common risk variants for autism spectrum disorder. They found genes related to ASD. This study also showed how the genes important for ASD relate to other symptoms/ traits. Interesting: negative relation between subjective well-being and ASD and chronotype and ASD. The lecture extensively explains how general news often misinterprets scientific articles and makes ridiculous strong claims. However, there are also real studies with surprising results: BEHAVIOR GENETICS IN PSYCHOLOGY - There is a strong link between fever during pregnancy and autism risk. Children that already were deceptable, and experienced the fever in the womb have a higher risk of autism → gene- environment interaction. - Exposure to lead during late pregnancy and early life correlates with autism risk. Attention-deficit/hyperactivity disorder (ADHD) Refers to children who exhibit very high activity, have a poor attention span, and act impulsively. ADHD is split into two parts; inattention part and hyperactivity part. Need at least 6 out of 9 symptoms to be diagnosed. Childs with ADHD more often have problems later in life, it increases the risk of self-damaging, genetic predisposition to addiction, memory loss, and an important finding is that it is not a childhood disorder, it is equally present in adults. The problem with ADHD is that it is still seen as dichotomous disorders, meaning you can only get medication if you reach a certain threshold. Officially, there is no bit of ADHD. Twin Studies ADHDIs highly heritable (71-73%) and very stable. Shows no shared environmental influence. It is the second most heritable childhood disorder (first is autism). Multivariate genetic research suggests that the components of activity and attention overlap genetically. An unusual aspect of ADHD results is that DZ correlations are often lower than expected relative to MZcorrelations, especially for parental ratings. This could be due to a contrast effect in which parents infate differences between their DZ twins, but this pattern of twin results is also consistent with nonadditive genetic variance. Nonadditive genetic variance: Individual differences due to nonlinear interactions between alleles at the same (dominance) or different (epistasis) loci. Effects of alleles or loci interact. Identifying genes Candidate gene studies of ADHD found two dopamine receptor genes that show small but significant associations; the dopamine receptors DRD4 and DRD5. Many GWA studies have been conducted for ADHDwith noclear and consistent findings. They do not really know the biological/genetic background of ADHD. Genes that increase the risk for development of ADHD; - A lower cognitive development and educational attainment. - Strong relationship to depression (high comorbidity), negative relation to wellbeing. - Positive relation to body size. - Strong positive relation to smoking; not because you have ADHD you want to calm down, but you are genetically sensitive to ADHD and thus also genetically sensitive to start smoking. - Sleeping problems: Overlap in genetic factors, we do not know if ADHD leads to sleeping problems or that genetically sensitive to ADHD and thus also sensitive to sleeping problems. Pre- and perinatal risk factors for ADHD are; cigarette exposure, alcohol exposure, low birth weight, psychosocial adversity and of course parental ADHD. Let’s look at the mechanisms of gene- environment interplay of prenatal smoking: Does prenatal smoking cause ADHD in children? - Heritability: The fact that the mother smokes is for 46% determined by genetics. Thus the fact that the mother continues smoking is partly determined by the genes and they transmit these genes to their children. - Gene-Environment Correlation → double disadvantage. Smokes during pregnancy (bad effect) and transmit genes to the child (bad effect). - Gene-Environment interaction → Even though many mothers smoke during pregnancy, only certain children are genetically sensitive to ADHD. - Epigenetics-> Smoking of the mother leads to changes in DNA methylation. Conclusion: Yes, there is a direct effect of prenatal substance use, especially in month 6-9. BEHAVIOR GENETICS IN PSYCHOLOGY Disruptive Behavior Disorders Criteria for conduct disorder include: Aggression, destruction of property, deceitfulness or theft, and other serious violations of rules such as running away from home. Genetic research suggests that conduct disorder is heterogeneous: - Aggressive conduct disorder shows substantial genetic influence and non-shared environmental influence. - Non-aggressive conduct disorder shows modest genetic influence and moderate shared environmental influence. There is also genetic heterogeneity in callous- unemotional personality: Involves psychopathic tendencies such as lack of empathy and guilt. A study showed that: - Antisocial behavior with callous- unemotional tendencies was highly heritable (80 percent), with no shared environmental influence. - Antisocial behavior without callous- unemotional tendencies was modestly heritable (30 percent) and showed moderate shared environmental influence. Anxiety Disorder Anxiety disorders affect one in eight children. Anxiety disorders also often co-occur with other disorders such as depression, eating disorders, and attention-deficit/ hyperactivity disorder (ADHD). This means that anxiety disorders also have high comorbidity. Comorbidity: When the presence of one disorder, increases the risk to develop another disorder. Twin studies of parental ratings of anxiety in childhood suggest an interestingly diverse pattern of results. - The highest heritability emerges for shyness, which is one of the most highly heritable personality traits. No environmental influence. - Heritability is also very high for obsessive- compulsive symptoms, although results in adulthood are more mixed. No environmental influence. - Heritability is more modest for generalized anxiety, which is comparable to results in adulthood. No environmental influence. In contrast, fears and especially separation anxiety are notable for evidence of shared environmental influence. Other disorders Some genetic influences have also been reported for childhood schizophrenia, childhood bipolar disorder, enuresis, and chronic tics, although much less genetic research has targeted these disorders. Solution? - High Heritability → Family intervention - Stable Heritability → Early intervention - Direct effects Prenatal Substance Use → Prevention - Gene-Environment Interplay → Childhood treatment - Genes->Personalized medicine Wellbeing, health psychology and aging Bioethics and the future of behavior genetics

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