Recent trends in  behavioural genetics  have indicated an additional focus toward researching the inheritance of human characteristics typically studied in  developmental psychology . For instance, a major focus in  developmental psychology  has been to characterize the influence of parenting styles on children. However, in most studies, genes are a  confounding  variable. Because children share half of their  alleles  with each parent, any observed effects of  parenting styles  could be effects of having many of the same alleles as a parent (e.g. harsh aggressive parenting styles have been found to correlate with similar aggressive child characteristics: is it the parenting or the genes?). Thus, behaviour genetics research is currently undertaking to distinguish the effects of the family environment from the effects of genes. This branch of behaviour genetics research is becoming more closely associated with mainstream  developmental psychology  and the sub-field of  developmental psychopathology  as it shifts its focus to the heritability of such factors as emotional  self-control , attachment, social functioning, aggressiveness, etc.


Several academic bodies exist to support behaviour genetic research, including the  International Behavioural and Neural Genetics Society ,  Behavior Genetics Association , the  International Society of Psychiatric Genetics , and the  International Society for Twin Studies . Behaviour genetic work features prominently in several more general societies, for instance the  International Behavioral Neuroscience Society .


Human behavioural geneticists use several designs to try to answer questions about the nature and mechanisms of genetic influences on behaviour. All of these designs are unified by being based around  human relationships  which disentangle genetic and environmental relatedness.


The cornerstone of behavioural genetics approaches is quantitative genetics theories, which were formulated more than half a century ago by geneticists concerned with the practical challenges of increasing economically relevant characteristics of domestic plants and animals. These methods are used to study a myriad of traits, including intelligence and other  cognitive abilities ,  personality traits  like extraversion and emotionality, and  psychiatric disorders  such as schizophrenia and bipolar disease. [ 3 ]


To examine genetic and environmental impacts on complex human behavioural traits, researchers uses three classic methods: family, twin, and adoption studies. Individual variations within the normal range of variation, as well as the genesis of psychopathologies, are investigated using each of these techniques.


Genes and shared (or familial) environmental factors have a role in family resemblance. The majority of familial research on schizophrenia are concerned with relative risk. Despite the fact that the scope of diagnosis varies, the lifetime risk of  schizophrenia  in the general population is generally stated as 1%. Siblings of people with schizophrenia, on the other hand, constitute 13% of the population [ which? ] . The hazards for second- and third-degree relatives are lower, at 3% and 2%, respectively, as predicted. In a  As a result, schizophrenia is certainly a familial trait. [ 3 ]


The basic understanding of behavioural genetics requires the separate study of effects of genes and environment influence on human behaviour. Such as, the genetic effects in a trait are discernible if pair of genetically identical (monozygotic twins) are much similar to one another than pair of genetically non-identical (dizygotic twin).


Twin and adoption studies describe the extent to which family resemblance is due to shared genes and the extent to which it is due to shared environments. Behavioral Scientist uses twin studies to examine hereditary and environmental influences on behavioural development.


For instance, some researchers also study adopted twins: the  adoption study . The adoption design produces estimates of various genetic and environmental components of variance, similar to the twin design. Furthermore, the adoption design facilitates


(1) the identification of specific environmental influences that are unaffected by heredity (e.g., the effects of life stressors),


(2) the analysis of heredity's role in ostensibly environmental relationships, and


(3) the evaluation of genotype-environment interactions and correlations. [ 3 ]


In this case the adoption disentangles the genetic relatedness of the twins (either 50% or 100%) from their family environments. Likewise the classic  twin study  contrasts the differences between  identical  and  fraternal twins  within a family compared to differences observed between families. This core design can be extended: the so-called "extended twin study" which adds additional family members, increasing power and allowing new genetic and environmental relationships to be studied. Excellent examples of this model are the Virginia 20,000 and the QIMR twin studies.


Generally, if the observed behaviour and cognitive traits have a genetic component, then genetically similar relatives resemble to each other as comparative to individuals who share lesser component of genome. I n case of environmental influence, researchers study the two broad classes of effects in behavioural genetics such as shared environmental factors causing them to behave similarly and the other one is nonshared environmental factors causing them to behave different from one another. For example, siblings raised together in same environment will have more evident shared environment influences whereas in relative siblings raised apart from each other will have non-shared environmental influence. The understanding of the effects of genes and the influence of shared and nonshared environment on human behaviour provides a comprehensive data for genetic and environmental relatedness. [ 3 ]


Also possible are the "children of twins" design (holding maternal genetic contributions equal across children with paternal genetics and family environments) and the "virtual twins" design - unrelated children adopted into a family who are very close or identical in age to biological children or other adopted children in the family. While the classical twin study has been  criticized  they continue to be of high utility. There are several dozen major studies ongoing, in countries as diverse as the US, UK, Germany, France, the  Netherlands , and Australia, and the method is used widely on phenotypes as diverse as  dental caries ,  body mass index ,  ageing ,  substance abuse ,  sexuality ,  cognitive abilities ,  personality ,  values , and a wide range of  psychiatric disorders . This is broad utility is reflected in several thousands of peer-review papers, and several dedicated societies and journals.


The approaches improve the capacity to specify and generalize results on the effects of genetic and environmental factors on characteristics and their evolution across time.


Quantitative trait locus  (QTL) analysis is a statistical approach for attempting to explain the genetic basis of variation in complex characteristics by linking two types of data: phenotypic data (trait measurements) and genotypic data (typically molecular markers).


Researchers in disciplines as diverse as  agriculture ,  biology , and  medicine  use QTL analysis to relate complicated traits to particular chromosomal regions. The purpose of this procedure is to determine the action, interaction, quantity, and type of action. The ability to disentangle the genetic component of complex characteristics has been enabled by QTL studies in model systems.


To research behavioural characteristics such as schizophrenia, bipolar disorder, alcoholism, and autism, large-scale national and international alliances have been constructed. Such partnerships will bring together enormous, consistently gathered samples, improving the likelihood of finding real susceptibility gene connections. [ 3 ]


The method is designed in collaboration of quantitative geneticists to enhance the capabilities to delineate between the genetic and environmental components of complex behavioural characteristics. Path analysis and structural equation modelling are two statistical approaches used in this methodology. The approach is used to see if genetic and environmental impacts can be employed in various populations. It would be useful to know how much of the total genetic variance—heritability—is accounted for by a limited selection of potential loci in studies of emotional stability, for example. [ 3 ]


In the context of the  nature-nurture debate ,  interactionism  is the view that all  human behavioral   traits  develop from the interaction of both "nature" and "nurture", that is, from both  genetic  and environmental factors. This view further holds that genetic and environmental influences on organismal development are so closely interdependent that they are inseparable from one another. [ 1 ]  Historically, it has often been confused with the  statistical  concept of  gene-environment interaction . [ 2 ]  Historically, interactionism has presented a limited view of the manner in which behavioral traits develop, and has simply demonstrated that "nature" and "nurture" are both necessary. [ 3 ]  Among the first biologists to propose an interactionist theory of development was  Daniel Lehrman . [ 4 ]  Since then, numerous interactionist perspectives have been proposed, and the contradictions between many of these perspectives has led to much controversy in  evolutionary psychology  and  behavioral genetics . [ 5 ] [ 6 ]  Proponents of various forms of interactionist perspectives include  Philip Kitcher , who refers to his view as "causal democracy", and  Susan Oyama , who describes her perspective as "constructive interactionism". [ 7 ]  Critics of interactionism include major figures in behavioral genetics such as  Arthur Jensen ,  Robert Plomin , and philosopher  Neven Sesardic . [ 8 ] [ 6 ] [ 9 ] [ 10 ]


Depression is not dependent entirely on genetic nor environmental influences alone to trigger its onset. Both genetic and environmental factors work accompanied to transform a vulnerability to depression to be expressed in its actuality. Research has demonstrated the synchrony of  polygenic scores  of major depressive disorders (MDD) with stressful life events and social support to increase the probability of developing depression. Although Monroe and Simons criticize interactionism for a lack of precise measurement to grasp its ‘conceptual essence’, there’s been numerous studies surrounding gene by environment interaction commonly focussing on  candidate genes  such as genetic variation within the  serotonin transporter  (SLC6A4) gene. [ 11 ]  As MDD is a polygenic trait its development is dependent on variations of a range of genes each exhibiting small effect sizes. Peyrot et al also found increased polygenic risk scores and genetic vulnerability in the presence of childhood trauma demonstrating the collaboration between environmental and genetic stressors. [ 12 ]


In the instance of personal life events however, whether they were passive or active trauma has a mediating effect on the  heritability  of the disorder. When passive, meaning the individual played less of an active in their trauma i.e., illness or accident, the  heritability  wasn’t as severe than when active i.e., in cases of separation, relationship conflict, financial or legal trouble. Contrarily, Mullins found whilst polygenic risk scores and stressful events were predictors of depression, however he believed them to be isolated factors acting independently. [ 13 ]


The combined therapy ( psychotherapy  with  pharmacotherapy ) for depression demonstrates statistically significant improvement compared with psychotherapy [ 14 ]  and pharmacotherapy. [ 15 ]  This is the value of considering both genetic and environmental factors in the explanation for depression. However, its effectiveness depends on the severity and chronicity of depression. For mild and moderate non-chronic depression, the combined therapy has no differences from a single therapy. [ 14 ]  Whilst results in the field are unreliable, research generally points in favour of the compatibility between genetic and environmental contributors to  psychopathology  and  depression . [ 16 ]


Ecological, biological, and residual stress pathways interact in order to manifest  post-traumatic stress disorder  (PTSD), the experience of trauma being the primary contributor to PTSD. The severity of trauma is a prime factor to the onset of PTSD but the question as to why only a fraction of individuals who experience trauma develop a pathological response whilst others do not rest in the assumptions that it is the combination of both genetic vulnerability that exhibit PTSD in alliance with environmental trauma. Among those who experience extreme severities of PTSD such as violent crimes, assault, severe accidents, approximately 3-35% develop symptoms. As inherent vulnerability increases the threshold for the environmental trauma to trigger the disorder decreases.


Residual stress is a key factor in the expression of PTSD, it is the initial and prolonged effects of trauma and a catalyst in its development. Ecological and biological pathways are also preceding factors that increase the likelihood of PTSD following trauma and residual stress. Ecological pathways include both personal and environmental influences such as coping mechanisms, interpersonal support, and the individual’s environment. And biological pathways include neurological anomalies, inherited traits, and structural anomalies such as hippocampal atrophy. Ecological and biological factors provide a predisposition whilst residual stress triggers its onset.


Greater trauma leads to greater levels of residual stress, and trauma can be divided into pre-trauma i.e., childhood abuse, and post-trauma i.e., social support, in which females are more influenced by post-trauma than their male counterparts in the development of PTSD. For example, survivors of sexual abuse found PTSD was influenced considerably by familial nature of support, negative parental reactions were found to intensify PTSD whereas high levels of social support helped diminish psychological fallout and recovery time.
Ecological pathways include factors such as a history of abuse, physical and sexual. Women with a history of physical abuse were found to be 5x more likely to have a history of PTSD, 10x more susceptible to experiencing it then controls. Parental abuse is a predictor for future anti-social behaviour and decreased social skills, and maladaptive  social information processing  increasing sensitivity to PTSD. These environmental factors aside from residual stress generate maladaptive cognitive patterns that provide a ‘breaking point’ to individuals with genetic vulnerability to PTSD to exhibit the disorder.


Biological pathways include a diversity of factors including hormonal and  neurotransmitter  abnormalities, and alterations in neural structure. Male adults of PTSD were found to have higher urinary biproduct of  norepinephrine  and epinephrine ( adrenaline ), lower  cortisol  levels, and abnormalities in neurotransmitter levels associated with anger, hostility and depression related to PTSD. Increased norepinephrine is involved with the activation of traumatic memories, and increased catecholamines are what lead to increased levels of stress-related hormones such as cortisol, and neurotransmitters associated with PTSD, which in the instance of trauma increases one’s vulnerability to it. Furthermore, structural alterations increase the susceptibility of PTSD, for example, sexually abused adolescent girls and those generally maltreated in comparison to a control group had dysregulation within their  hypothalamic pituitary adrenal axis  (HPA) alongside decreased hippocampal volume. Furthermore,  corticotropin releasing hormone  (CRH) increases heart rate and enhances fear conditioning and is also the hormone responsible for regulating the HPA axis which corresponds with symptoms of PTSD. [ 17 ]


Twin studies that investigated the development of schizophrenia found that identical twins have a higher  concordance rate  for schizophrenia than non-identical twins. [ 18 ] [ 19 ] [ 20 ]  However, none of them found a 100% concordance rate from identical twins. Identical twins have exact genes. This suggests the development of schizophrenia is not only due to genetic factors but also environmental factors. On the other hand, in an adoption study, participants were adopted at a young age by families without a schizophrenia history. Children with genetic risks (such as having a genetic schizophrenia mother) were more sensitive to negative child-raring styles than those with no genetic risk. They are more likely to develop schizophrenia in undesirable child-raring style families. [ 21 ]  This suggests the role of genetic factors in the development of schizophrenia. Therefore, researchers consider the interaction of genetic and environmental factors to explain schizophrenia. This is also the tendency of psychologists to research mental disorders.


The diathesis-stress model is an interactionism approach. In the context of schizophrenia, diathesis is the  vulnerability . Vulnerabilities can be either  genetic predisposition  or early experiences, or both. [ 22 ]  Stressors are any event that can trigger a schizophrenia-vulnerable individual to the onset of the condition. [ 23 ] [ 24 ] [ 25 ]  This interactionism approach explains why people with similar genes or traumatic experiences, do not necessarily develop schizophrenia together.


The early diathesis-stress model was developed by Meehl. [ 26 ]  It suggested that diathesis was a single gene, called schizogene. It led to a personality development, called schizotypic personality. Individuals who did not have schizotypic personality would not express the symptoms of schizophrenia, no matter what stress they experienced. However, once a schizotypic personality, the stress from the family could trigger schizophrenia. This model is over-simple. First, more recent research found that 108 genes are associated with the development of schizophrenia. [ 27 ]  No schizogene determines schizophrenia, it is a  polygenic  mental disorder. [ 18 ]  Second, the stressors are not limited to the problematic family environment. They can be any negative experience in life. [ 28 ]  For example, childhood traumas, low socioeconomic status, substance misuse…


However, the concept of the diathesis-stress model did not be given up. Researchers make it more comprehensive. The research suggests that genetic defect leads to biological vulnerability. [ 25 ]  This schizophrenia–vulnerable individual’s dopamine (DA) receptors and hippocampus area were abnormal. Later, stressful experiences (the stressor) can activate their hypothalamic pituitary adrenal (HPA) axis. [ 24 ] [ 25 ]  This leads to the release of cortisol. This release of cortisol can further disrupt that abnormal DA system. According to the  dopamine hypothesis , the DA system abnormality is associated with the symptoms of schizophrenia. Stressors also further damage the hippocampus of vulnerable individuals. Schizophrenia patients have a smaller volume of the hippocampus compared with a typical brain [ 18 ] [ 29 ] [ 25 ]  Moreover, stressors also cause patient more sensitive to stress in everyday life, [ 23 ] [ 25 ]  this is a vicious cycle. Therefore, the stressors are not just a trigger of schizophrenia but also lead to deterioration.


In the more comprehensive model, diathesis is not just genetic. Early childhood traumas can also lead to psychological vulnerability. [ 18 ] [ 30 ] [ 31 ] [ 23 ]  This traumatic experience can be child abuse and neglect. For example, Read found that 69% of women and 59% of male schizophrenia patients experienced childhood abuse (physical abuse, sexual abuse or both). [ 30 ]  This experience impacts the early development of the brain. For example, disrupts the HPA, DA and hippocampal systems. [ 31 ]  This can create a similar vulnerability to that created by genes.


Similarly, stressors are not just subjective negative life experiences. For example, using cannabis can be a stressor that triggers schizophrenia-vulnerable individuals to develop schizophrenics. [ 32 ] [ 33 ]  Houston [ 33 ]  found that sexual abuse had a significant correlation with the development of schizophrenia, only if the patients used cannabis. This can be because cannabis influences the dopamine system. [ 22 ]  However, to the patients, the reason for using substances such as cannabis is for enjoyment. [ 34 ] [ 35 ]  Therefore, stressors are now defined as all events that can trigger vulnerable individuals to express schizophrenia symptoms. However, not all smokers develop schizophrenia. Thus, using cannabis is only considered as a stressor but not a cause.


The diathesis-stress model supports a reason for using combined therapy for schizophrenia treatment. [ 28 ] [ 31 ]  If not approved the interactionism approach, there is no reason to use the combined therapy. For example, if therapists propose schizophrenia is due to genetic reasons. Then, it is difficult to convince the patients to participate in drug treatment followed by psychological treatment, and vice versa. However, combined therapy demonstrates statistically significant improvement in reducing schizophrenia symptoms compared to a single treatment. [ 36 ] [ 37 ] [ 38 ]  Although it did not indicate the effect of reducing the relapse rate.


Recent research has a better understanding of the diathesis-stress model to explain schizophrenia.  However, the mechanism by which vulnerability and stressors contribute to the development of schizophrenia remains unclear. [ 22 ]  Therefore, the interactionist treatment (combined therapy) just simply combines psychotherapy and pharmacotherapy. This may be attributed to the reason why combined therapy does not always have statistically significant improvement in mitigating schizophrenia symptoms compared to drug therapy. [ 36 ] [ 37 ]  In the case of combined therapy, it is more expensive than a single therapy. This unstable effectiveness can impact its promotion because it lacks cost-effectiveness.


Moreover, the significant improvement of the combined therapy can simply be because the effect of their own is added up. It does not necessarily mean there is an interaction effect between these two treatments. There can be a treatment causation fallacy. [ 22 ]


The  Minnesota Center for Twin and Family Research  ( MCTFR ) is a series of  behavioral genetic   longitudinal studies  of families with twin or adoptive offspring conducted by researchers at the  University of Minnesota . [ 1 ]  It seeks to identify and characterize the genetic and environmental influences on the development of  psychological  traits.


Principal investigators include  Matt McGue ,  William Iacono , and Kevin Haroian.


The primary cohorts of participants include the Minnesota Twin Family Study, Sibling Interaction and Behavior Study, Minnesota Twin Registry, and a variety of other cohorts of participants. [ 1 ]


MTFS is a  twin study  established in June 1989 with 1300 same-gendered twin pairs age 11 or 17, with an additional cohort of 500 such pairs recruited around 2004. Twins were born between 1972 and 2000. [ 1 ]  All twins born in Minnesota at that time were eligible to participate using birth registry data.  Both identical and fraternal twins share certain aspects of their environment.  This allows researchers to estimate the relative impact of environmental and genetic  influences on  phenotypes . The focus of the MTFS is on behavioral phenotypes, such as academic outcomes, cognitive abilities, personality, and interests; family and social relationships; mental and physical health; physiological measurements. The assessment wave structure and protocol are similar to the Sibling Interaction and Behavior Study (below), allowing the use of complementary twin and adoption designs to address  behavioral genetic  questions.


The Minnesota Twin Registry was established in 1983. [ 2 ]  Its original goal was to establish a  registry  of all twins born in Minnesota from 1936 to 1955 to be used for psychological research. Recently, it has added twins born between 1961 and 1964. It primarily conducts personality and interests tests with its 8,000+ twin pairs and family members via mail. From this project, it was able to confirm that twins and their families are representative of the population and that a poll of their opinions would be more accurate than polls in the newspaper.


The Sibling Interaction and Behavior Study (SIBS) is a study of >600 adoptive and non-adoptive families. [ 1 ]  The  adoption study  design allows one to disentangle the environmental and genetic influences on a  phenotype , including psychological phenotypes. The assessment wave structure and protocol are similar to the Minnesota Twin Family Study, allowing the use of complementary study designs to answer a given question.


The Minnesota Study of Twins Reared Apart was a twin study conducted at the University of Minnesota, independent of the Minnesota Center for Twin and Family Research. In 1979,  Thomas J. Bouchard  began to study twins who were separated at birth and reared in different families. He found that an identical twin reared away from his or her co-twin seems to have about an equal chance of being similar to the co-twin in terms of personality, interests, and attitudes as one who has been reared with his or her co-twin. [ 3 ]  Bouchard has said that these two twins happened to be unusually alike, while most twins show more differences: [ 4 ]


There probably are genetic influences on almost all facets of human behavior, but the emphasis on the idiosyncratic characteristics is misleading. On average, identical twins raised separately are about 50 percent similar – and that defeats the widespread belief that identical twins are carbon copies. Obviously, they are not. Each is a unique individual in his or her own right.


Psychologists now refer to studies such as this as an Adoption Strategy. [ 5 ] [ 6 ]   Partial funding for the study was obtained through a research grant from the  Pioneer Fund . [ 7 ]


Misbehaving Science: Controversy and the Development of Behavior Genetics  is a 2014 book about the history of  behavior genetics . It was written by  University of California, Los Angeles  sociologist  Aaron Panofsky , and was published by the  University of Chicago Press . It won the 2015 President's Book Award from the  Social Science History Association . [ 1 ]


In  Misbehaving Science , Panofsky argues that  eugenics  was reinvented in the mid-20th century as behavior genetics, and that this was done in the hope of curing many social problems such as  crime  and  homelessness . [ 2 ]  He refers to behavior genetics as "misbehaving science" because, according to him, the standards of scientific inquiry in this field are vague enough to allow political and social ideologies to affect scientific conclusions. As he put it in the book: "If science is like a machine for resolving controversies, in misbehaving science that machine is broken." [ 3 ]  Panofsky also contends that behavior geneticists have reacted to disappointing research results in  molecular genetics  by simply lowering their expectations. [ 4 ]


Reviews of  Misbehaving Science  were published in  the British Journal for the History of Science , [ 5 ]   New Genetics and Society , [ 6 ]   Medical Anthropology Quarterly , [ 7 ]  the  Journal of the History of Biology , [ 8 ]   Science, Technology & Society , [ 9 ]  and  Developmental Psychobiology . [ 10 ]


New Scientist ' s Kate Douglas wrote that in  Misbehaving Science , Panofsky tells the story of the development of behavior genetics "with wonderful insight". [ 2 ]  Tal Arbel of  Tel Aviv University  wrote that the book "offers an original, sharply intelligent and timely analysis of the historical conditions, social mechanisms and cultural forces" that led to the development of behavior genetics. [ 5 ]  Another favorable review appeared in  New Genetics and Society , where  Northwestern University  sociologist Mariana Craciun described the book as "detailed and compelling". [ 6 ]  In her review of the book, Nicole C. Nelson of the  University of Wisconsin–Madison  wrote that "The conclusions Panofsky reaches are specific to the field of behavior genetics, but his approach offers insights that are potentially applicable to many other fields. His exemplary handling of different levels of analysis would make this text especially useful for a graduate-level methods course." [ 7 ]  In a review published in the  Journal of the History of Biology , Hallam Stevens also praised the book, writing that Panofsky's "...empirically rich and provocative account of the history of behavior genetics gives us a compelling example of how a discipline can propel itself by courting controversy, drumming up attention, and rehashing old arguments." [ 8 ]


Neurogenetics  studies the role of  genetics  in the development and function of the  nervous system . It considers neural characteristics as  phenotypes  (i.e. manifestations, measurable or not, of the genetic make-up of an individual), and is mainly based on the observation that the nervous systems of individuals, even of those belonging to the same  species , may not be identical. As the name implies, it draws aspects from both the studies of  neuroscience  and genetics, focusing in particular how the genetic code an organism carries affects its expressed  traits .  Mutations  in this genetic sequence can have a wide range of effects on the quality of life of the individual. Neurological diseases, behavior and personality are all studied in the context of neurogenetics. The field of neurogenetics emerged in the mid to late 20th century with advances closely following advancements made in available technology. Currently, neurogenetics is the center of much research utilizing cutting edge techniques.


The field of neurogenetics emerged from advances made in molecular biology, genetics and a desire to understand the link between genes, behavior, the brain, and neurological disorders and diseases. The field started to expand in the 1960s through the research of  Seymour Benzer , considered by some to be the father of neurogenetics. [ 1 ]


His pioneering work with  Drosophila  helped to elucidate the link between circadian rhythms and genes, which led to further investigations into other behavior traits. He also started conducting research in neurodegeneration in fruit flies in an attempt to discover ways to suppress neurological diseases in humans. Many of the techniques he used and conclusions he drew would drive the field forward. [ 2 ]


Early analysis relied on statistical interpretation through processes such as  LOD  (logarithm of odds) scores of  pedigrees  and other observational methods such as affected sib-pairs, which looks at phenotype and  IBD  (identity by descent) configuration. Many of the disorders studied early on including  Alzheimer's ,  Huntington's  and  amyotrophic lateral sclerosis  (ALS) are still at the center of much research to this day. [ 3 ]  By the late 1980s new advances in genetics such as  recombinant DNA  technology and  reverse genetics  allowed for the broader use of  DNA polymorphisms  to test for linkage between DNA and gene defects. This process is referred to sometimes as linkage analysis. [ 4 ] [ 5 ]  By the 1990s ever advancing technology had made genetic analysis more feasible and available. This decade saw a marked increase in identifying the specific role genes played in relation to neurological disorders. Advancements were made in but not limited to:  Fragile X syndrome , Alzheimer's,  Parkinson's ,  epilepsy  and ALS. [ 6 ]


While the genetic basis of simple diseases and disorders has been accurately pinpointed, the genetics behind more complex, neurological disorders is still a source of ongoing research. New developments such as the  genome wide association studies  (GWAS) have brought vast new resources within grasp. With this new information genetic variability within the human population and possibly linked diseases can be more readily discerned. [ 7 ]  Neurodegenerative diseases are a more common subset of neurological disorders, with examples being  Alzheimer's disease  and  Parkinson's disease . Currently no viable treatments exist that actually reverse the progression of neurodegenerative diseases; however, neurogenetics is emerging as one field that might yield a causative connection. The discovery of linkages could then lead to therapeutic drugs, which could reverse brain degeneration. [ 8 ]


One of the most noticeable results of further research into neurogenetics is a greater knowledge of gene loci that show linkage to neurological diseases. The table below represents a sampling of specific gene locations identified to play a role in selected neurological diseases based on prevalence in the  United States . [ 9 ] [ 10 ] [ 11 ] [ 12 ]


Logarithm of odds (LOD)  is a statistical technique used to estimate the probability of gene linkage between traits. LOD is often used in conjunction with pedigrees, maps of a family's genetic make-up, in order to yield more accurate estimations.  A key benefit of this technique is its ability to give reliable results in both large and small sample sizes, which is a marked advantage in laboratory research. [ 14 ] [ 15 ]


Quantitative trait loci (QTL)  mapping is another statistical method used to determine the chromosomal positions of a set of genes responsible for a given trait.  By identifying specific genetic markers for the genes of interest in a  recombinant inbred strain , the amount of interaction between these genes and their relation to the observed phenotype can be determined through complex statistical analysis.
In a neurogenetics laboratory, the phenotype of a model organisms is observed by assessing the morphology of their brain through thin slices. [ 16 ]   QTL mapping can also be carried out in humans, though brain morphologies are examined using  nuclear magnetic resonance imaging (MRI)  rather than brain slices. Human beings pose a greater challenge for QTL analysis because the genetic population cannot be as carefully controlled as that of an inbred recombinant population, which can result in sources of statistical error. [ 17 ]


Recombinant DNA  is an important method of research in many fields, including neurogenetics.  It is used to make alterations to an organism's genome, usually causing it to over- or under-express a certain gene of interest, or express a mutated form of it.  The results of these experiments can provide information on that gene's role in the organism's body, and it importance in survival and fitness. The hosts are then screened with the aid of a toxic drug that the selectable marker is resistant to. The use of recombinant DNA is an example of a reverse genetics, where researchers create a mutant genotype and analyze the resulting phenotype.  In  forward genetics , an organism with a particular phenotype is identified first, and its genotype is then analyzed. [ 18 ] [ 19 ]


Model organisms are an important tool in many areas of research, including the field of neurogenetics.  By studying creatures with simpler nervous systems and with smaller genomes, scientists can better understand their biological processes and apply them to more complex organisms, such as humans.  Due to their low-maintenance and highly mapped genomes, mice,  Drosophila , [ 20 ]  and  C. elegans [ 21 ]  are very common.   Zebrafish [ 22 ]  and  prairie voles [ 23 ]  have also become more common, especially in the social and behavioral scopes of neurogenetics.


In addition to examining how genetic mutations affect the actual structure of the brain, researchers in neurogenetics also examine how these mutations affect cognition and behavior. One method of examining this involves purposely engineering model organisms with mutations of certain genes of interest. These animals are then classically conditioned to perform certain types of tasks, such as pulling a lever in order to gain a reward. The speed of their learning, the retention of the learned behavior, and other factors are then compared to the results of healthy organisms to determine what kind of an effect – if any – the mutation has had on these higher processes. The results of this research can help identify genes that may be associated with conditions involving cognitive and learning deficiencies. [ 24 ]


Many research facilities seek out volunteers with certain conditions or illnesses to participate in studies. Model organisms, while important, cannot completely model the complexity of the human body, making volunteers a key part to the progression of research. Along with gathering some basic information about medical history and the extent of their symptoms, samples are taken from the participants, including blood,  cerebrospinal fluid , and/or muscle tissue. These tissue samples are then genetically sequenced, and the genomes are added to current database collections. The growth of these data bases will eventually allow researchers to better understand the genetic nuances of these conditions and bring therapy treatments closer to reality. Current areas of interest in this field have a wide range, spanning anywhere from the maintenance of  circadian rhythms , the progression of neurodegenerative disorders, the persistence of periodic disorders, and the effects of mitochondrial decay on metabolism. [ 25 ]


Such databases are used in  genome-wide association studies  (GWAS). Examples of phenotypes investigated by notable neurogenetics GWAS include:


Advances in  molecular biology  techniques and the species-wide  genome project  have made it possible to map out an individual's entire genome. Whether genetic or environmental factors are primarily responsible for an individual's personality has long been a topic of debate. [ 28 ] [ 29 ]  Thanks to the advances being made in the field of neurogenetics, researchers have begun to tackle this question by beginning to map out genes and correlate them to different personality traits. [ 28 ]  There is little to no evidence to suggest that the presence of a  single  gene indicates that an individual will express one style of behavior over another; rather, having a specific gene could make one more predisposed to displaying this type of behavior.  It is starting to become clear that most genetically influenced behaviors are due to the effects of many variants within  many  genes, in addition to other neurological regulating factors like neurotransmitter levels.  Due to fact that many behavioral characteristics have been conserved across species for generations, researchers are able to use animal subjects such as mice and rats, but also fruit flies, worms, and zebrafish, [ 20 ] [ 21 ]  to try to determine specific genes that correlate to behavior and attempt to match these with human genes. [ 30 ]


While it is true that variation between species can appear to be pronounced, at their most basic they share many similar behavior traits which are necessary for survival. Such traits include mating, aggression, foraging, social behavior and sleep patterns. This conservation of behavior across species has led biologists to hypothesize that these traits could possibly have similar, if not the same, genetic causes and pathways. Studies conducted on the genomes of a plethora of organisms have revealed that many organisms have  homologous genes , meaning that some genetic material has been  conserved  between species.  If these organisms shared a common evolutionary ancestor, then this might imply that aspects of behavior can be inherited from previous generations, lending support to the genetic causes – as opposed to the environmental causes – of behavior. [ 29 ]  Variations in personalities and behavioral traits seen amongst individuals of the same species could be explained by differing levels of expression of these genes and their corresponding proteins. [ 30 ]


There is also research being conducted on how an individual's genes can cause varying levels of  aggression  and aggression control  [ citation needed ] .


Throughout the animal kingdom, varying styles, types and levels of aggression can be observed leading scientists to believe that there might be a genetic contribution that has conserved this particular behavioral trait. [ 31 ]  For some species varying levels of aggression have indeed exhibited direct correlation to a higher level of  Darwinian fitness . [ 32 ]


A great deal of research has been done on the effects of genes and the formation of the brain and the central nervous system. The following wiki links may prove helpful:


There are many genes and proteins that contribute to the formation and development of the central nervous system, many of which can be found in the aforementioned links. Of particular importance are those that code for  BMPs , BMP inhibitors and  SHH . When expressed during early development, BMP's are responsible for the differentiation of epidermal cells from the ventral  ectoderm . Inhibitors of BMPs, such as  NOG  and  CHRD , promote differentiation of ectoderm cells into prospective neural tissue on the dorsal side. If any of these genes are improperly regulated, then proper formation and differentiation will not occur.
BMP also plays a very important role in the patterning that occurs after the formation of the  neural tube . Due to the graded response the cells of the neural tube have to BMP and Shh signaling, these pathways are in competition to determine the fate of preneural cells. BMP promotes dorsal differentiation of pre-neural cells into  sensory neurons  and Shh promotes ventral differentiation into  motor neurons . There are many other genes that help to determine neural fate and proper development include,  RELN ,  SOX9 ,  WNT ,  Notch and Delta coding genes ,  HOX , and various cadherin coding genes like  CDH1  and  CDH2 . [ 33 ]


Some recent research has shown that the level of gene expression changes drastically in the brain at different periods throughout the life cycle.  For example, during prenatal development the amount of  mRNA  in the brain (an indicator of gene expression) is exceptionally high, and drops to a significantly lower level not long after birth.  The only other point of the life cycle during which expression is this high is during the mid- to late-life period, during 50–70 years of age.  While the increased expression during the prenatal period can be explained by the rapid growth and formation of the brain tissue, the reason behind the surge of late-life expression remains a topic of ongoing research. [ 34 ]


Neurogenetics is a field that is rapidly expanding and growing.  The current areas of research are very diverse in their focuses.  One area deals with molecular processes and the function of certain proteins, often in conjunction with cell signaling and neurotransmitter release, cell development and repair, or neuronal plasticity.  Behavioral and cognitive areas of research continue to expand in an effort to pinpoint contributing genetic factors. As a result of the expanding neurogenetics field a better understanding of specific neurological disorders and phenotypes has arisen with direct correlation to  genetic mutations . With severe disorders such as  epilepsy , brain malformations, or  mental retardation  a single  gene  or causative condition has been identified 60% of the time; however, the milder the intellectual handicap the lower chance a specific genetic cause has been pinpointed.  Autism  for example is only linked to a specific, mutated gene about 15–20% of the time while the mildest forms of mental handicaps are only being accounted for genetically less than 5% of the time. Research in neurogenetics has yielded some promising results, though, in that mutations at specific gene loci have been linked to harmful phenotypes and their resulting disorders. For instance a  frameshift mutation  or a  missense mutation  at the  DCX  gene  location causes a neuronal migration defect also known as  lissencephaly . Another example is the  ROBO3  gene where a mutation alters  axon  length negatively impacting neuronal connections. Horizontal gaze palsy with progressive scoliosis (HGPPS) accompanies a mutation here. [ 35 ]  These are just a few examples of what current research in the field of neurogenetics has achieved. [ 36 ]


NM_001161363 NM_001161364 NM_012428 NM_017455


NM_001293673 NM_009145 NM_001357751


NP_001154835 NP_001154836 NP_036560 NP_059429


NP_001280602 NP_033171 NP_001344680 NP_001392991


Neuroplastin  is a  protein  that in humans is encoded by the  NPTN   gene . [ 5 ] [ 6 ] [ 7 ]


Neuroplastin is a  type I transmembrane protein  belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions. The alpha and beta transcripts show differential localization within the brain. [ 7 ]


In 2014, in a study led by Dr.  Sylvane Desrivières , of  King's College London 's  Institute of Psychiatry  found that "teenagers who had a highly functioning NPTN gene performed better in intelligence tests" [ 8 ] [ 9 ] [ 10 ]


This article on a  gene  on human  chromosome 15  is a  stub . You can help Wikipedia by  expanding it .


Psychiatric genetics  is a subfield of  behavioral neurogenetics  and  behavioral genetics  which studies the role of genetics in the development of  mental disorders  (such as  alcoholism ,  schizophrenia ,  bipolar disorder , and  autism ). The basic principle behind psychiatric genetics is that genetic  polymorphisms  (as indicated by linkage to e.g. a  single nucleotide polymorphism ) are part of the  causation  of  psychiatric disorders . [ 1 ]


Psychiatric genetics is a somewhat new name for the old question, "Are behavioral and psychological conditions and deviations inherited?". [ 2 ]  The goal of psychiatric genetics is to better understand the  causes of psychiatric disorders , to use that knowledge to improve treatment methods, and possibly also to develop personalized treatments based on genetic profiles (see  pharmacogenomics ). In other words, the goal is to transform parts of psychiatry into a  neuroscience -based discipline. [ 3 ]


Recent advances in  molecular biology  allowed for the identification of hundreds of common and rare genetic variations that contribute to psychiatric disorders. [ 4 ]


Research on psychiatric genetics began in the late nineteenth century with  Francis Galton  (a founder of psychiatric genetics) who was motivated by the work of  Charles Darwin  and his concept of desegregation. These methods of study later improved due to the development of more advanced clinical, epidemiological, and biometrical research tools. Better research tools were the precursor to the ability to perform valid family, twin, and  adoption studies . Researchers learned that genes influence how these disorders manifest and that they tend to aggregate in families. [ 2 ] [ 5 ]


Most psychiatric disorders are highly  heritable ; the estimated heritability for  bipolar disorder ,  schizophrenia , and  autism  (80% or higher) is much higher than that of diseases like  breast cancer  and  Parkinson disease . [ 1 ]  Having a close family member affected by a mental illness is the largest known risk factor, to date. [ 6 ]  However,  linkage analysis  and  genome-wide association studies  have found few reproducible  risk factors . [ 1 ]


Heterogeneity  is an important factor to consider when dealing with genetics. Two types of heterogeneity have been identified in association with psychiatric genetics: causal and clinical. Causal heterogeneity refers to a situation in which two or more causes can independently induce the same clinical syndrome. Clinical heterogeneity refers to when a single cause can lead to more than one clinical syndrome. [ 7 ]


Several genetic risk factors have been found with the  endophenotypes  of psychiatric disorders, rather than with the diagnoses themselves. That is, the risk factors are associated with particular symptoms, not with the overall diagnosis. [ 1 ]  In psychiatry,  endophenotypes  are a way of objectively measuring certain internal processes  in a reliable way that is often lacking the diseases with which they are associated. [ 8 ]  They lie in the space between genes and disease process and allow for some understanding of the biology of psychiatric diseases. [ 8 ]


A systematic comparative analysis of shared and unique genetic factors highlighted key gene sets and molecular processes underlying six major neuropsychiatric disorders:  attention deficit hyperactivity disorder ,  anxiety disorders ,  autistic spectrum disorders ,  bipolar disorder ,  major depressive disorder , and  schizophrenia . [ 9 ]  This may ultimately translate into improved diagnosis and treatment of these debilitating disorders.


Linkage ,  association , and  microarray  studies generate raw material for findings in psychiatric genetics. [ 10 ]
 Copy number variants  have also been associated with psychiatric conditions. [ 11 ]


Genetic Linkage studies attempt to find a correlation between the diagnosis and inheritance of certain alleles within families who have two or more ill relatives. An analysis of a linkage study uses a wide chromosomal region, whereas a genetic association study endeavors to identify a specific DNA  polymorphism , which can be a deletion, inversion, or repletion of a sequence. [ 12 ]  Case-control association studies can be used as an exploratory tool for narrowing the area of interest after preliminary mapping of a gene by a linkage study. [ 13 ]


One hope for future  genetic testing  is the ability to test for presymptomatic or prenatal illnesses. This information has the potential to improve the lives of those affected with certain illnesses, specifically those like  schizophrenia . If possible to test for schizophrenia before the symptoms develop, proactive interventions could be developed, or even preventative treatments. [ 7 ]  In one study, 100% of patients with bipolar disorder indicated that they would probably take a genetic test to determine they were carrying a gene associated with the disorder, if such a test existed. [ 6 ]


Francis Galton  studied both desirable and undesirable behavioral and mental properties to better examine the world of genetics. His research led to his proposal of a  eugenic  program of birth control. [ 14 ]  His goal was to decrease the frequency of the less desirable traits that occurred throughout the population. His ideas were pursued by psychiatrists in many countries such as the United States, Germany and Scandinavia. [ 2 ] [ 15 ]


Genotyping and its implications are still seen as ethically controversial by many people. [ who? ]  The  ELSI  (Ethical, Legal, and Social Initiative), which is part of the  Human Genome Project , was created with the aim of "foster[ing] basic and applied research on the ethical, legal and social implications of genetic and genomic research for individuals, families and communities.". [ 16 ]


A  reeler  is a  mouse   mutant , so named because of its characteristic "reeling"  gait . This is caused by the profound underdevelopment of the mouse's  cerebellum , a segment of the brain responsible for  locomotion . The mutation is  autosomal  and  recessive , and prevents the typical cerebellar  folia  from forming.


Cortical neurons are generated normally but are abnormally placed, resulting in disorganization of cortical laminar layers in the  central nervous system . The reason is the lack of  reelin , an  extracellular matrix   glycoprotein , which, during the corticogenesis, is secreted mainly by the  Cajal–Retzius cells .
In the reeler neocortex, cortical plate neurons are aligned in a practically inverted fashion ("outside-in"). In the ventricular zone of the cortex fewer neurons have been found to have radial glial processes. [ 1 ]  In the  dentate gyrus  of  hippocampus , no characteristic radial glial scaffold is formed and no compact  granule cell  layer is established. [ 2 ]  Therefore, the reeler mouse presents a good model in which to investigate the mechanisms of establishment of the precise neuronal network during development.


There are two types of the reeler mutation:


In order to unravel the reelin signaling chain, attempts are made to cut the signal downstream of reelin, leaving reelin expression intact but creating the reeler  phenotype , sometimes a partial phenotype, thus confirming the role of downstream molecules. The examples include:


Heterozygous reeler mice, also known as  HRM , while lacking the apparent phenotype seen in the homozygous reeler, also show some brain abnormalities due to the reelin deficit.


Heterozygous (rl/+) mice express reelin at 50% of wild-type levels and have grossly normal brains but exhibit a progressive loss during aging of a neuronal target of reelin action,  Purkinje cells . [ 15 ]


The mice have reduced density of  parvalbumin -containing  interneurons  in circumscribed regions of  striatum , according to one study. [ 16 ]


Studies reveal a 16% deficit in the number of Purkinje cells in 3-month-old (+/rl) and a 24% one in 16-month-old animals: surprisingly this deficit is only present in the (+/rl) males, while the females are spared.


First mention of reeler mouse mutation dates back to 1951. [ 17 ]  In the later years, histopathological studies revealed that the reeler cerebellum is dramatically decreased in size and the normal  laminar organization  found in several brain regions is disrupted (Hamburgh, 1960). In 1995, the RELN gene and  reelin  protein were discovered at chromosome 7q22 by Tom Curran and colleagues. [ 18 ]


In  behavioral genetics , the  Scarr–Rowe effect , also known as the  Scarr–Rowe hypothesis , refers to the proposed  moderating  effect of low  socioeconomic status  on the  heritability of children's IQ . According to this hypothesis, lower socioeconomic status and greater exposure to social disadvantage during childhood leads to a decrease in the heritability of IQ, as compared to children raised in more advantaged environments. [ 1 ]  It is considered an example of  gene–environment interaction . [ 2 ] [ 3 ]  This hypothesized effect was first proposed by  Sandra Scarr , who found support for it in a 1971 study of  twins  in  Philadelphia , and these results were replicated by  David C. Rowe  in 1999. [ 4 ] [ 5 ]  Since then, similar results have been replicated numerous times, though not all replication studies have yielded positive results. A 2015 meta-analysis found that the effect was predominant in the United States while less evident in societies with robust child welfare systems. [ 1 ]


In  Sandra Scarr 's original work, she outlines the methods behind the study of genetic and environmental variance, using data from the 1960 US  Census  tract to estimate  Socioeconomic status  (SES), [ 6 ]  and the  Iowa Tests of Basic Skills  to study genetic and environmental variations across children from advantaged and disadvantaged populations. This study focussed on the heritability of IQ based on social class and race, with the social and racial groups being too variated to make generalizations between groups questionable. Across both races, the total variance was generally found to be greater in the groups of higher socioeconomic status. It is suggested that, while genetic factors are not as significant in determining aptitude in lower SES groups of either race, there is a larger variance in  phenotypes  among higher SES children. [ 7 ]


One of the major limitations of Scarr's original work is that the sample of twins was separated into same-sex and opposite-sex as opposed to  monozygotic  (MZ) and  dizygotic  (DZ), a method which undermined the statistical power of this study. [ 8 ]


Fischbein used data from a longitudinal study started from the Department of Educational Research at the  Stockholm Institute of Education , with twins from 40 of the largest cities and towns in Sweden. [ 9 ]  An estimation of Socioeconomic status (SES) was taken from the parents' occupation and family income, and scores were gathered from the sample using a differential ability test (DBA) that included a verbal ability test, inductive reasoning test, and a clerical speed test. [ 10 ] [ 11 ]  The clerical speed test showed insignificant differences between the social groups. Heritability of all variables tested, including IQ, was significantly higher in the higher SES group compared to the lower SES group, which presented the lowest heritability. [ 12 ]


David C. Rowe 's work looks at the influence of genetic and environmental factors specifically on the variation of verbal IQ, with data from the 1909 sibling pairs from the  National Longitudinal Study of Adolescent Health . Parental education level was used as a moderator for this study. It was found that verbal IQ was highly heritable among children whose parents had a higher level of education, by being similar to the earlier studies of Fischbein and Scarr-Salapatek, this adds support to the hypothesis of variance in IQ heritability at different levels of socioeconomic status. It is acknowledged that the level of parental education is likely to be influenced by genetic factors, with higher-educated parents passing on a higher level of IQ. [ 13 ]


In 2003,  Eric Turkheimer  and colleagues replicated the effect in an analysis of the  National Collaborative Perinatal Project . Medical, psychological, and SES data were collected for children at 8 months, 1 year, 4 years, and 7 years; at age 7 they completed the  Wechsler Intelligence Scale for Children  (WISC). The mothers' SES data were collected at their registration in the study and again at the end of the 7-year study. The study found that the variance in IQ in relation to SES displayed a non-linear relationship, suggesting that children from low SES families may have environmental and genetic differences, and differences in poorer environments are likely to contribute more to variations in genetic outcome than differences in higher SES environments. [ 14 ]


McLloyd's 1998 study looked at socioeconomic disadvantage and the impact it could have on child development as a whole, IQ being included. This provided a separation of socioeconomic disadvantage into two types of  poverty : persistent and transitory. These were then compared to an advantageous socioeconomic status. Persistent poverty was shown to have the worst impact on IQ, as well as other aspects of child development when compared to transitory poverty and children who never experience poverty. This study acknowledged other variables that were likely to be associated with a low SES (for example  chronic stress , harsh and inconsistent parenting, etc.). [ 15 ]


While there have been many replications, the Scarr–Rowe effect has primarily been studied in  American  samples [ 16 ]  and has been less applicable in  European  samples; this is likely due to more even access to economic resources, including educational, limiting poverty. [ 17 ]
In 2019, a study of  German  twins by Gottschling tested the  heritability  of cognitive ability at three mean age points – 11, 17, and 23 years old. It was found that, in the younger cohorts of 11 and 17, higher SES could be correlated with a significantly higher mean level of cognitive ability. This provided support for the original study during childhood and  adolescence , although not to quite the same degree. [ 18 ]


The original theory hypothesizes that higher SES will be associated with greater heritability of IQ, very few studies have addressed this interaction within adult populations. [ 19 ]  Evidence from Gottschling's 2019 study suggests that the influence of the SES of a family as a moderator for IQ heritability changes as people get older – with results showing the effect being less significant in adolescence and not shown present in adulthood. [ 20 ]  A 2015  meta-analysis  of 14 studies found similar evidence that the Scarr–Rowe effect diminishes with age. [ 1 ]


The same 2015 meta-analysis found evidence of the Scarr–Rowe effect only in  the United States , but no evidence of such an effect in  Australia  or  Western Europe . [ 1 ]  Turkheimer et al. (2015) similarly note that the effect has been replicated more in the United States than in other countries, and that even in the United States some studies have failed to replicate it. Based on their analysis of the Louisville Twin Study, they reported weak evidence for the hypothesis that was not  statistically significant . [ 21 ]  A 2016 study in Australia found no evidence for the Scarr–Rowe effect. [ 22 ]


In 2017, a twin study with a sample of 24,620 twins and 274,786 siblings born and raised in the economically diverse US state of Florida also found no evidence of the Scarr–Rowe effect. [ 23 ]


Scrambler  is a spontaneous mouse  mutant  lacking a functional  DAB1  gene, resulting in a  phenotype  resembling that seen in the  reeler  mouse. [ 1 ]  The strain was first described by Sweet  et al.  in 1996. [ 2 ]


The spontaneous  autosomal   recessive  scrambler mutation on  chromosome 4  causes a deficiency of  DAB1 , encoding disabled-1, a protein involved in the signaling of the  Reelin  protein, lacking in the  reeler  mutant, [ 3 ]  Dab1-scm homozygous mutants possess a reeler-like phenotype with respect to cell malpositioning in  cerebellar cortex ,  hippocampus , and  neocortex . [ 4 ] [ 5 ]   Purkinje cell  and  granule cell  degeneration results in  ataxia . [ 6 ]  Despite normal Reln mRNA levels, Dab1-scm mutants have defective reelin signaling, indicating that disabled-1 acts downstream of reelin. Cell ectopias are identical with targeted disruption of Dab1. [ 7 ] [ 8 ]


Dab1-scm mutants have a widespread gait obvious to the naked eye ( ataxia ). In their home-cage, they often reel and fall, especially when attempting to rear up against the walls. Nevertheless, the mutants are fertile, and so can be reproduced from one generation to the next. Relative to non-ataxic controls of the same background strain, Dab1-scm mutants were impaired in the  Rotarod Performance test  of motor coordination and a grid-climbing test. [ 9 ]  When picked up by the tail, they show a pathological reflex, limb-clasping, characterized by holding together fore- or hind-limbs, or all four together in a bat-like posture. [ 10 ]


Dab1-scm mutants were distinguished from non-ataxic controls as early as postnatal day 8 based on body tremor, gait anomalies, and body weight. [ 11 ]  On postnatal day 15, motor coordination deficits were evident on horizontal bar and inclined or vertical grid tests in association with a weaker grip strength. Further differences were detected on postnatal day 22 and evaluation at the adult age revealed impairments indicative of permanent motor alterations.


As adults, Dab1(scm) mutants showed motor coordination impairments on stationary beam, coat-hanger, and rotorod tests but were more active in the open-field. Dab1(scm) mutants were also less anxious in the elevated plus-maze but with higher latencies in the emergence test. In mutants versus controls, changes in regional brain metabolism as measured by cytochrome oxidase (COX) activity occurred mainly in structures intimately connected with the cerebellum. [ 12 ]


In addition to motor deficits, adult Dab1-scm mutants are characterized by anomalies in grooming behavior, in particular shorter grooming bouts than non-ataxic controls of the same background strain, though they display the normal cephalocaudal sequence of grooming anterior body parts (face washing and forelimb licking) prior to posterior parts. [ 13 ]  Dab1-scm mutants are also characterized by reduced spontaneous alternation rates and deficits in visuomotor control while swimming towards a visible platform. [ 14 ]


In  adoption studies ,  selective placement  refers to the practice by which  adoption agencies  tend to deliberately match certain characteristics of an adopted child's adopted parents with those of his or her biological parents. When this occurs, it results in a correlation between environments between biological relatives raised in different homes. It has the potential to bias the conclusions of such studies, because twins who were reared in separate environments may in fact have been reared in much more similar environments than assumed. This can result in an inflated estimate of  heritability . [ 1 ] [ 2 ] [ 3 ]  There is evidence that selective placement was a major  confound  in many early studies of twins reared apart. [ 4 ]  Some adoption studies report little or no evidence of selective placement. [ 1 ] [ 5 ] [ 6 ] [ 7 ]  For example, a 1979 study by Ho et al. reported a generally low level of selective placement in adopted children for either physical or behavioral traits. The authors concluded that to the extent that selective placement occurred for such traits, "our data suggest that it is based largely on characteristics of the birth father," rather than those of the adoptee. [ 8 ]  Carey (2003) concluded that selective placement was "moderate" for physical characteristics and typically "small or nonexistent" for behavioral characteristics. [ 9 ]


This  psychology -related article is a  stub . You can help Wikipedia by  expanding it .


Shiverer  mice  are  mice  which possess the  shiverer  (shi/shi) mutation in the  MBP  gene.  Shiverer  mice develop a characteristic "shaking" or "shivering" gait within a few weeks of birth. They are commonly used as animal models of  leukodystrophy  in  neuroscience  research.


The  shiverer  mutation is an  autosomal recessive   loss-of-function  mutation. It was generated by a 20-kilobase deletion within the  MBP  gene, [ 1 ]  resulting in the failure of  oligodendrocytes  to form compact  myelin  in the  central nervous system .  Axons  in  shiverer  mice fail to attain a normal diameter and exhibit altered  cytoskeleton  structure. [ 2 ]


Approximately twelve days after birth,  shiverer  mice begin to exhibit  tremors  which progressively worsen. They exhibit  tonic seizure  behavior after weaning and die prematurely, typically between 50 and 100 days after birth. [ 3 ]


Shiverer  mice are used to model human  leukodystrophies  due to the congenital nature and early onset of the  shiverer  phenotype, which mimics the disease progression observed in humans. They are also used to study myelin defects more generally in  demyelinating diseases  such as  multiple sclerosis .


The  shiverer  model has also been used to test novel therapies which promote  myelination  such as  neural stem cell  therapy. [ 4 ]


Sticky mouse  is a  murine  possessing a gene mutation in the enzyme  alanyl-tRNA synthetase  (AARS). [ 1 ]  The sticky mouse, with this particular mutation, presents a good model in which to investigate mechanisms of  neuronal degeneration . Its most immediately obvious symptom is a sticky secretion on the mouse's fur (thus the name); however, it is accompanied by lack of muscle control,  ataxia ,  alopecia , loss of  Purkinje cells  in the  cerebellum , and eventually, death.


Sticky  mouse  is one of several  animal  mutants that are known to have problems in  mRNA  translation and are used in studies. [ 2 ]


Tryon's Rat Experiment  is a  psychology  experiment conducted by  Robert Tryon  in 1940 and published in the  Yearbook of the National Society for Studies in Education. [ 1 ]


Prior to  Robert Tryon ’s study of selective rat breeding, concluded in 1942, many psychologists believed that environmental, rather than genetic, differences produced individual behavioral variations.  Tryon sought to demonstrate that genetic traits often did, in fact, contribute to behavior.  To do so, Tryon created an experiment that tested the proficiency of successive generations of rats in completing a maze. He initiated the experiment by exposing a genetically diverse group of rats to the maze, labeling those who made the fewest errors “bright”, and those with the most errors “dull”.  Tryon then mated the “bright” males with “bright” females, and “dull” males with “dull” females.  After their children matured, Tryon repeated the maze test with them, and again separated the “bright” and the “dull”, again breeding “bright” with “bright” and “dull” with “dull”. Tryon continued this process for seven generations, creating two distinct breeds of “bright” and “dull” rats. In order to demonstrate that behavior had little effect on the genetically selectively bred rats, and lessen the chance of error when making his conclusions, Tryon cross-fostered the rats—that is, he had a “dull” mother raise “bright” children, and vice versa.  The independent variables in his experiment were the parental pairings, the choice of environment and parents for upbringing, and number of rats put through the maze. The dependent variable was the number of errors made by the rats in 19 trials of the maze. [ 2 ]


While Tryon's results showed that the “bright" rats made significantly fewer errors in the maze than the “dull" rats did, the question exists of what other sensory, motor, motivational, and learning processes also influenced the results of the experiment.  A common misconception of this experiment and other similar experiments is that the observed change in the performance in the maze directly correlates with general learning ability.  This is not the case.  Rather, it has become a widely accepted belief among behavior geneticists that the superiority of the bright rats may have been confined to Tryon’s specific test; thus, it is not necessarily due to a difference in learning capacity between the two groups of rats.  Genetic variation, such as better  peripheral vision , can make some rats “bright” and others “dull”, but does not determine their intelligence. [ 3 ]  Nonetheless, Tryon’s famous rat-maze experiment demonstrated that the difference between rat performances was genetic since their environments were controlled and identical. [ 4 ]


Twin studies  are studies conducted on  identical  or  fraternal  twins. They aim to reveal the importance of environmental and  genetic  influences for traits,  phenotypes , and disorders. Twin research is considered a key tool in  behavioral genetics  and in related fields, from biology to psychology. Twin studies are part of the broader methodology used in  behavior genetics , which uses all data that are genetically informative –  siblings  studies, adoption studies, pedigree, etc. These studies have been used to track traits ranging from personal behavior to the presentation of severe mental illnesses such as  schizophrenia .


Twins are a valuable source for observation because they allow the study of environmental influence and varying  genetic makeup : "identical"  or  monozygotic  (MZ)  twins  share essentially 100% of their genes, which means that most differences between the twins (such as height, susceptibility to boredom, intelligence, depression, etc.) are due to experiences that one twin has but not the other twin. [ 1 ]  "Fraternal" or  dizygotic  (DZ) twins share only about 50% of their genes, the same as any other sibling. Twins also share many aspects of their environment (e.g., uterine environment, parenting style, education, wealth, culture, community) because they are born into the same family.  The presence of a given genetic or phenotypic trait in only one member of a pair of identical twins (called discordance) provides a powerful window into environmental effects on such a trait.


Twins are also useful in showing the importance of the unique environment (specific to one twin or the other) when studying trait presentation. Changes in the unique environment can stem from an event or occurrence that has only affected one twin. This could range from a head injury or a birth defect that one twin has sustained while the other remains healthy.


The classical twin design compares the similarity of monozygotic (identical) and dizygotic (fraternal) twins. If identical twins are considerably more similar than fraternal twins (which is found for most traits), this implies that genes play an important role in these traits. By comparing many hundreds of families with twins, researchers can then understand more about the roles of genetic effects, shared environment, and unique environment in shaping behavior.


Modern twin studies have concluded that all studied  traits  are partly influenced by  genetic  differences, with some characteristics showing a stronger influence (e.g.  height ), others an intermediate level (e.g.  personality traits ) and some more complex  heritabilities , with evidence for different genes affecting different aspects of the trait – as in the case of  autism . [ 2 ]


Twins  have been of interest to scholars since early civilization, including the early physician  Hippocrates  (5th century BCE), who attributed different diseases in twins to different material circumstances, [ 3 ]  and the stoic philosopher  Posidonius  (1st century BCE), who attributed such similarities to shared astrological circumstances. [ 4 ]


Gustav III , King of  Sweden  was the first to  commission  a medical study using identical twins. [ citation needed ] [ original research? ]  Gustav's father,  Adolph Frederick  had been an opponent of stimulating drinks such as  tea  and  coffee , signing the  Misuse and Excesses Tea and Coffee Drinking Edict  in 1757. [ 5 ]  Both Gustav III and his father had read and been strongly influenced by a 1715 treatise from a  French  physician on the dangers of what would later be identified as  caffeine  in tea and coffee. [ 6 ]  After assuming the throne in 1771 the king became strongly motivated to demonstrate to his subjects that coffee and tea had deleterious effects on human health. To this end he offered to commute the death sentences of a pair of twin murderers if they participated in a primitive  clinical trial .


Both condemned men agreed and subsequently spent the rest of their lives in prison fulfilling the king's demands: that one twin drink three pots of coffee every day and the other three pots of tea. The tea drinking twin died first at the age of 83, long after Gustav III, who was  assassinated in 1792 . The age of the coffee-drinking twin at his death is unknown, as both doctors assigned by the king to monitor this study predeceased him. The ban on coffee and tea in Sweden was lifted in 1823. [ 7 ] [ 8 ]


A more recent study is from  Sir Francis Galton's  pioneering use of twins to study the role of genes and environment on  human development  and behavior. Galton, however, was unaware of the difference between  identical  and  DZ  twins. [ 9 ]  This factor was still not understood when the first study using psychological tests was conducted by  Edward Thorndike  (1905) using fifty pairs of twins. [ 10 ] [ 11 ]  This paper was an early statement of the hypothesis that family effects decline with age. His study compared twin pairs age 9–10 and 13–14 to normal siblings born within a few years of one another.


Thorndike incorrectly reasoned that his data supported for there being one, not two, twin types. This mistake was repeated by  Ronald Fisher  (1919), who argued


The preponderance of twins of like sex, does indeed become a new problem, because it has been formerly believed to be due to the proportion of identical twins. So far as I am aware, however, no attempt has been made to show that twins are sufficiently alike to be regarded as identical really exist in sufficient numbers to explain the proportion of twins of like sex. [ 12 ]


An early, and perhaps first, study understanding the distinction is from the  German  geneticist  Hermann Werner Siemens  in 1924. [ 13 ]  Chief among Siemens' innovations was the  polysymptomatic similarity diagnosis . This allowed him to account for the oversight that had stumped Fisher, and was a staple in twin research prior to the advent of molecular markers.


Wilhelm Weinberg  and colleagues in 1910 used the identical-DZ distinction to calculate respective rates from the ratios of same- and opposite-sex twins in a maternity population. They partitioned co-variation amongst relatives into genetic and environmental elements, anticipating the later work of  Fisher  and  Wright , including the effect of dominance on similarity of relatives, and beginning the first classic-twin studies. [ 14 ]


A study conducted by  Darrick Antell  and Eva Taczanowski found that "twins showing the greatest discrepancies in visible aging signs also had the greatest degree of discordance between personal lifestyle choices and habits", and concluded that "the genetic influences on aging may be highly overrated, with lifestyle choices exerting far more important effects on physical aging." [ 15 ]


Examples of prominent twin studies include the following:


The power of twin designs arises from the fact that twins may be either identical ( monozygotic  (MZ), i.e. developing from a single fertilized egg and therefore sharing all of their  polymorphic   alleles ) or fraternal ( dizygotic  (DZ), i.e. developing from two fertilized eggs and therefore sharing on average 50% of their alleles, the same level of genetic similarity found in non-twin siblings). These known differences in genetic similarity, together with a testable assumption of equal environments for identical and fraternal twins, [ 16 ]  creates the basis for the design of twin studies aimed at estimating the overall effects of genes and environment on a phenotype. [ 17 ] [ 18 ]


The basic logic of the twin study can be understood with very little mathematical knowledge beyond an understanding of the concepts of  variance  and thence derived  correlation .


Like all behavior genetic research, the  classical twin study  begins by assessing the variance of behavior (called a  phenotype  by geneticists) in a large group, and attempts to estimate how much of this is due to:


Typically these three components are called  A  (additive genetics)  C  (common environment) and  E  (unique environment); hence the acronym  ACE . It is also possible to examine non-additive genetics effects (often denoted  D  for dominance ( ADE model ); see below for more complex twin designs).


The  ACE model  indicates what proportion of variance in a trait is heritable, versus the proportion due to a shared environment or unshared environment. Research is typically carried out using  Structural equation modeling  (SEM) programs such as   OpenMx  capable in principle of handling all sorts of complex pedigrees. However the core logic underlying such programs is the same as the one underlying the twin design described here.


Monozygotic (identical – MZ) twins raised in a family share 100% of their genes, and all of their shared environment. Any differences arising between them in these circumstances are random (i.e. due to environmental effects unique to each twin). The correlation between identical twins provides an estimate of  A  +  C . Dizygotic (DZ) twins also share C, but share, on average only 50% of their genes: so the correlation between fraternal twins is a direct estimate of ½ A + C . If we denote with  r  the  correlation , we can define  r mz  and  r dz  as the correlations of a trait among identical and fraternal twins, respectively. For any particular trait, then:


Stated again, the difference between these two sums then allows us to solve for  A  and  C  (and as a consequence, for  E ). As the difference between the identical and fraternal correlations is due entirely to a halving of the genetic similarity, the additive genetic effect  A  is twice the difference between the identical and fraternal correlations:


given the estimate for  A , the one for  C  can be derived, for instance, from the first equation:


Finally, since the trait correlation among identical twins reflects the full contribution of  A  and  C , the residual variation  E  can be estimated by subtracting this correlation from 1


To summarize therefore, the additive genetic factor  A  is twice the difference between MZ and DZ twin correlations (this is known as  Falconer's formula ),  C  is the MZ twin correlation minus this estimate of  A , and the random (unique) factor  E  is (1 -  r mz ), i.e. MZ twins differ due to unique environments only (Jinks & Fulker, 1970; Plomin, DeFries, McClearn, & McGuffin, 2001).


Beginning in the 1970s, research transitioned to  modeling   genetic, environmental effects using  maximum likelihood  methods (Martin & Eaves, 1977). While computationally much more complex, this approach has numerous benefits rendering it almost universal in current research.


An example structural model (for the heritability of height among Danish males) [ 19 ]  is shown:


Model A on the left shows the raw variance in height. This is useful as it preserves the absolute effects of genes and environments, and expresses these in natural units, such as mm of height change. Sometimes it is helpful to standardize the parameters, so each is expressed as percentage of total variance. Because we have decomposed variance into A, C, and E, the total variance is simply A + C + E. We can then scale each of the single parameters as a proportion of this total, i.e., Standardised–A = A/(A + C + E). Heritability is the standardised genetic effect.


A principal benefit of modeling is the ability to explicitly compare models: Rather than simply returning a value for each component, the modeler can compute  confidence intervals  on parameters, but, crucially, can drop and add paths and test the effect via statistics such as the  AIC . Thus, for instance to test for predicted effects of family or shared environment on behavior, an AE model can be objectively compared to a full ACE model. For example, we can ask of the figure above for height: Can C (shared environment) be dropped without significant loss of fit? Alternatively,  confidence intervals  can be calculated for each path.


Multivariate modeling can give answers to questions about the genetic relationship between variables that appear independent. For instance: do IQ and long-term memory share genes? Do they share environmental causes? Additional benefits include the ability to deal with interval, threshold, and continuous data, retaining full information from data with missing values, integrating the latent modeling with measured variables, be they measured environments, or, now, measured molecular genetic markers such as  SNPs . In addition, models avoid constraint problems in the crude correlation method: all parameters will lie, as they should, between 0–1 (standardized).


Multivariate, and multiple-time wave studies, with measured environment and repeated measures of potentially causal behaviours are now the norm. Examples of these models include extended twin designs, [ 20 ] [ 21 ]  simplex models, [ 22 ]  and growth-curve models. [ 23 ]


SEM  programs such as  OpenMx [ 24 ]  and other applications suited to constraints and multiple groups have made the new techniques accessible to reasonably skilled users.


As MZ twins share both their genes and their family-level environmental factors, any differences between MZ twins reflect E: the unique environment. Researchers can use this information to understand the environment in powerful ways, allowing  epidemiological  tests of causality that are otherwise typically confounded by factors such as gene–environment covariance,  reverse causation  and  confounding .


An example of a positive MZ discordant effect is shown below on the left. The twin who scores higher on trait 1 also scores higher on trait 2. This is compatible with a "dose" of trait 1 causing an increase in trait 2. Of course, trait 2 might also be affecting trait 1. Disentangling these two possibilities requires a different design (see below for an example). A null result is incompatible with a causal hypothesis.


Take for instance the case of an observed link between depression and exercise (See Figure above on right). People who are depressed also reporting doing little physical activity. One might  hypothesise  that this is a  causal  link: that "dosing" patients with exercise would raise their mood and protect against depression. The next figure shows what empirical tests of this hypothesis have found: a null result. [ 25 ]


Longitudinal discordance designs


As may be seen in the next Figure, this design can be extended to multiple measurements, with consequent increase in the kinds of information that one can learn. This is called a cross-lagged model (multiple traits measured over more than one time). [ 26 ]


In the longitudinal discordance model, differences between identical twins can be used to take account of relationships among differences across traits at time one (path A), and then examine the distinct hypotheses that increments in trait1 drive subsequent change in that trait in the future (paths B and  E), or, importantly, in other traits (paths C & D). In the example, the hypothesis that the observed  correlation  where  depressed  persons often also  exercise  less than average is causal, can be tested. If exercise is protective against depression, then path D should be significant, with a twin who exercises more showing less depression as a consequence.


It can be seen from the modeling above, the main assumption of the twin study is that of equal family environments, also known as the  equal environments assumption . [ 27 ] [ 28 ] [ 29 ]  A special ability to test this assumption occurs where parents believe their twins to be non-identical when in fact they are genetically identical. Studies of a range of psychological traits indicate that these children remain as concordant as MZ twins raised by parents who treated them as identical. [ 30 ]


Molecular genetic methods of heritability estimation have tended to produce lower estimates than classical twin studies due to modern SNP arrays not capturing the influence of certain types of variants (e.g., rare variants or repeat polymorphsisms), though some have suggested it is because twin studies overestimate heritability. [ 31 ]  A 2016 study determined that the assumption that the prenatal environment of twins was equal was largely tenable. [ 32 ]  Researchers continue to debate whether or not the equal environment assumption is valid. [ 33 ] [ 34 ] [ 35 ] [ 36 ] [ 37 ]


A particularly powerful technique for testing the twin method was reported by Visscher  et al. [ 38 ]  Instead of using twins, this group took advantage of the fact that while siblings on average share 50% of their genes, the actual gene-sharing for individual sibling pairs varies around this value, essentially creating a continuum of genetic similarity or "twinness" within families. Estimates of heritability based on direct estimates of gene sharing confirm those from the twin method, providing support for the assumptions of the method.


Genetic factors, including both gene expression and the range of gene × environment interactions, may differ between the sexes. Fraternal opposite sex twin pairs are invaluable in explicating these effects.


In an extreme case, a gene may only be expressed in one sex (qualitative sex limitation). [ clarification needed ]  More commonly, the effects of particular alleles may depend on the sex of the individual. A gene might cause a change of 100 g in weight in males, but perhaps 150 g in females – a quantitative gene effect.


Environments may impact on the ability of genes to express themselves and may do this via sex differences. For instance, genes affecting voting behavior would have no effect in females if females are excluded from the vote. More generally, the logic of sex-difference testing can extend to any defined sub-group of individuals. In cases such as these, the correlation for same and opposite sex DZ twins will differ, betraying the effect of the sex difference.


For this reason, it is normal to distinguish three types of fraternal twins.  A standard analytic workflow would involve testing for sex-limitation by fitting models to five groups, identical male, identical female, fraternal male, fraternal female, and fraternal opposite sex. Twin modeling thus goes beyond correlation to test causal models involving potential causal variables, such as sex.


Gene effects may often be dependent on the environment. Such interactions are known as  G×E interactions , in which the effects of a gene allele differ across different environments. Simple examples would include situations where a gene multiplies the effect of an environment: perhaps adding 1 inch to height in high nutrient environments, but only half an inch to height in low-nutrient environments. This is seen in different slopes of response to an environment for different genotypes.


Often researchers are interested in changes in  heritability  under different conditions: In environments where  alleles  can drive large phenotypic effects (as above), the relative role of genes will increase, corresponding to higher heritability in these environments.


A second effect is  G × E correlation , in which certain alleles tend to accompany certain environments. If a gene causes a parent to enjoy reading, then children inheriting this allele are likely to be raised in households with books due to GE correlation: one or both of their parents has the allele and therefore will accumulate a book collection  and  pass on the book-reading allele. Such effects can be tested by measuring the purported environmental correlate (in this case books in the home) directly.


Often the role of environment seems maximal very early in life, and decreases rapidly after  compulsory education  begins. This is observed for instance in reading [ 39 ]
as well as intelligence. [ 40 ]  This is an example of a G*Age effect and allows an examination of both GE correlations due to parental environments (these are broken up with time), and of G*E correlations caused by individuals actively seeking certain environments. [ 41 ]


Studies in plants or in  animal breeding  allow the effects of experimentally randomized  genotypes  and environment combinations to be measured. By contrast, human studies are typically observational. [ 42 ] [ 43 ]  This may suggest that  norms of reaction  cannot be evaluated. [ 44 ] [ 45 ]


As in other fields such as  economics  and  epidemiology , several designs have been developed to capitalise on the ability to use differential gene-sharing, repeated exposures, and measured exposure to environments (such as children social status, chaos in the family, availability and quality of education, nutrition, toxins etc.) to combat this confounding of causes. An inherent appeal of the classic twin design is that it begins to untangle these confounds. For example, in identical and fraternal twins shared environment and genetic effects are  not confounded, as they are in non-twin familial studies. [ 18 ]  Twin studies are thus in part motivated by an attempt to take advantage of the random assortment of genes between members of a family to help understand these correlations.


While the twin study tells us only how genes and families affect behavior within the observed range of environments, and with the caveat that often genes and environments will covary, this is a considerable advance over the alternative, which is no knowledge of the different roles of genes and environment whatsoever. [ 46 ]  Twin studies are therefore often used as a method of controlling at least one part of this observed variance: Partitioning, for instance, what might previously  have been assumed to be family environment into shared environment and additive genetics using the experiment of fully and partly shared genomes in twins. [ 46 ]  Additional information is available outside the classic twin design.  Adoption designs  are a form of natural experiment that tests norms of reaction by placing the same genotype in different environments. [ 47 ]  Association studies, e.g., [ 48 ]  allow direct study of allelic effects.   Mendelian randomization  of alleles also provides opportunities to study the effects of alleles at random with respect to their associated environments and other genes. [ 49 ]


The basic or classical twin-design contains only identical and fraternal twins raised in their biological family. This represents only a sub-set of the possible genetic and environmental relationships. It is fair to say, therefore, that the heritability estimates from twin designs represent a first step in understanding the genetics of behavior.


The variance partitioning of the twin study into additive genetic, shared, and unshared environment is a first approximation to a complete analysis taking into account  gene–environment covariance  and  interaction , as well as other non-additive effects on behavior. The revolution in  molecular genetics  has provided more effective tools for describing the genome, and many researchers are pursuing molecular genetics in order to directly assess the influence of  alleles  and environments on traits.


An initial limitation of the twin design is that it does not afford an opportunity to consider both Shared Environment and Non-additive genetic effects simultaneously. This limit can be addressed by including additional siblings to the design.


A second limitation is that gene–environment correlation is not detectable as a distinct effect unless it is added to the model. Addressing this limit requires incorporating adoption models, or children-of-twins designs, to assess family influences uncorrelated with shared genetic effects.


While concordance studies compare traits either present or absent in each twin,  correlational  studies compare the agreement in continuously varying traits across twins.


The twin method has been subject to criticism from statistical  genetics , statistics and  psychology , with some researchers, such as Burt & Simons (2014), arguing that conclusions reached via this method are ambiguous or meaningless. [ 50 ]  Core elements of these criticisms and their rejoinders are listed below.


Critics of twin studies argue that they are based on false or questionable assumptions, including that monozygotic twins share 100% of their genes [ 51 ]  and the equal environments assumption. [ 52 ] [ 53 ]  On this basis, critics contend that twin studies tend to generate inflated or deflated estimates of heritability due to biological  confounding factors  and consistent underestimation of environmental variance. [ 50 ] [ 54 ]  Other critics take a more moderate stance, arguing that the equal environments assumption is typically inaccurate, but that this inaccuracy tends to have only a modest effect on heritability estimates. [ 55 ]


Peter Schönemann  criticized methods for estimating  heritability  developed in the 1970s. He has also argued that the heritability estimate from a twin study may reflect factors other than shared  genes . Using the statistical models published in  Loehlin  and Nichols (1976), [ 56 ]  the narrow HR-heritability of responses to the question "did you have your back rubbed"  has been shown to work out to .92 heritable for males and .21 heritable for females, and the question "Did you wear sunglasses after dark?" is 130% heritable for males and 103% for females. [ 57 ] [ 58 ]  Critics also contend that the concept of "heritability" estimated in twin studies is merely a statistical abstraction with no relationship to the underlying DNA [ 59 ]  and that the  statistical  underpinnings of twin research are invalid. Statistical critiques argue that  heritability  estimates used for most twin studies rest on restrictive assumptions that are usually not tested, and if they are, they are often contradicted by the data.


Before computers, statisticians used methods that were computationally tractable, at the cost of known limitations. Since the 1980s these approximate statistical methods have been discarded. Modern twin methods based on  structural equation modeling  are not subject to the limitations and heritability estimates such as those noted above are mathematically impossible. [ 60 ]
Critically, the newer methods allow for explicit testing of the role of different pathways and incorporation and testing of complex effects. [ 46 ]


Results of twin studies cannot be automatically generalized beyond the population they come from. It is therefore important to understand the particular sample studied, and the nature of twins themselves. Twins are not a  random sample  of the population, and they differ in their developmental environment. In this sense they are not representative. [ 61 ]


For example: Dizygotic (DZ) twin births are affected by many factors. Some women frequently produce more than one  egg  at each  menstrual  period and are therefore more likely to have twins. This tendency may run in the  family  either on the mother's or father's side, and often runs through both. Women over the age of 35 are more likely to produce two eggs. Women who have three or more children are also likely to have dizygotic twins. Artificial induction of  ovulation  and in  vitro   fertilization - embryo  replacement can also give rise to fraternal and identical twins. [ 62 ] [ 63 ] [ 64 ] [ 65 ] [ 66 ] [ 67 ]


However, twins differ very little from non-twin siblings. Measured studies on the personality and intelligence of twins suggest that they have scores on these traits very similar to those of non-twins (for instance Deary et al. 2006).


Separated twin pairs, identical or fraternal, are generally separated by  adoption . This makes their families of origin non-representative of typical twin families in that they give up their children for adoption. The families they are adopted to are also non-representative of typical twin families in that they are all approved for adoption by children's protection authorities and that a disproportionally large fraction of them have no biological children. Those who volunteer to studies are not even representative of separated twins in general since not all separated twins agree to be part of twin studies. [ 68 ] [ 69 ]


There can be some issues of undetected behaviors in the case of behaviors that many people keep secret presently or in their earlier lives. They may not be as willing to reveal behaviors that are discriminated against or stigmatized. If environment played no role in the actual behavior, skewed detection would still make it look like it played a role. For environment to appear to have no role in such cases, there would have to be either a counterproductivity of intolerance in the sense of intolerance causing the behavior it is bigoted against, or a flaw in the study that makes the results scientifically useless. Even if environment plays no role, the numbers would still be skewed. [ 70 ] [ 71 ] [ 72 ]


For a group of twins,  pairwise concordance  is defined as C/(C+D), where C is the number of concordant pairs and D is the number of discordant pairs.