Twin study
Encyclopedia
Twin studies help disentangle the relative importance of environmental and genetic
influences on individual traits and behaviors. Twin research is considered a key tool in behavioral genetics and related fields. Alternate groups that can also be studied based on facts about genetic similarity include full siblings in general and adoptees
.
Twins are a valuable source for observation due to their genotypes and family environments tending to be similar. More specifically, monozygotic (MZ) or "identical" twin
s, share nearly 100% of their genetic polymorphisms
, which means that most variation in pairs' traits (measured height, susceptibility to boredom, intelligence, depression, etc.) is due to their unique experiences. Dizygotic (DZ) or "fraternal" twins share only about 50% of their polymorphisms. DZ twins are helpful to study because they tend to share many aspects of their environment (e.g., uterine environment, parenting style, education, wealth, culture, community) by virtue of being born in the same time and place.
The classical twin design compares the similarity of MZ (identical) and DZ (fraternal) twins. MZ twins are almost always more similar than DZ twins due to higher genetic similarity coupled with the same amount of environmental similarity. By comparing many hundreds of families of twins, researchers can then understand more about the complementary roles of genetic effects, shared environment, and unique environment in shaping people.
Modern twin studies have shown that almost all traits are in part influenced by genetic
differences, with some characteristics showing a strong influence (e.g. height
), others an intermediate level (e.g. intelligence quotient) and some more complex heritabilities
, with evidence for different genes affecting different aspects of the trait - as in the case of autism
.
While twins
have been of interest to scholars since early civilization, such as the early physician Hippocrates
(5th c. BCE
), who attributed similar diseases in twins to shared material circumstances , and the stoic philosopher Posidonius
(1st c. BCE), who attributed such similarities to shared astrological circumstances , the modern history of the twin study derives 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 critical genetic difference between MZ and DZ twins.
This factor was still not understood when the first study using psychological tests was conducted by Edward Thorndike
(1905) using 50-pairs of twin. Notably this paper was perhaps the first statement of the idea (formulated as a testable hypothesis) that C (family effects) decline with age: comparing 9-10 and 13-14 year old twin-pairs, and normal siblings born within a few years of one another.
Fatefully, however, Thorndike incorrectly reasoned that his data gave support for there being one, not two types of twins: Missing the critical distinction that makes within-family twin studies such a powerful resource in psychology and medicine. This mistake was repeated by Ronald Fisher
(1919), who argued
The first published twin study utilizing the distinction between MZ and DZ twins is sometimes cited as that of the German
geneticist Hermann Werner Siemens
in 1924. Chief among Siemens' innovations was the "polysymptomatic similarity diagnosis". This allowed him to overcome the barrier that had stumped Fisher and was a staple in twin research prior to the advent of molecular markers. Wilhelm Weinberg
, however, had already by 1910 used the MZ-DZ distinction to calculate their respective rates from the ratios of same- and opposite-sex twins in a maternity population, worked out partitioning of covariation amongst relatives into genetic and environmental elements (anticipating Fisher
and Wright
) including the effect of dominance on relative's similarity, and begun the first classic-twin studies.
s) – or dizygotic (DZ: developing from two fertilized eggs and therefore sharing on average 50% of their polymorphic
alleles, the same level of genetic similarity as found in non-twin siblings). These known differences in genetic similarity, together with a testable assumption of equal environments for MZ and DZ twins (Bouchard & Propping, 1993) creates the basis for the twin design for exploring the effects of genetic and environmental variance on a phenotype (Neale & Cardon, 1992).
The basic logic of the twin study can be understood with very little mathematics beyond an understanding of correlation
and the concept of variance
.
Like all behavior genetic research, the classic twin study begins from assessing the variance of a behavior (called a phenotype
by geneticists) in a large group, and attempts to estimate how much of this is due to genetic effects (heritability
), and how much appears to be due to shared or unique environmental effects - events that affect each twin in a different way, or events that occur to one twin but not another.
Typically these three components are called A (additive genetics) C (common environment) and E (unique environment); the so-called ACE Model. It is also possible to examine non-additive genetics effects (often denoted D for dominance (ADE model
); see below for more complex twin designs).
Given the ACE model, researchers can determine what proportion of variance in a trait is heritable, versus the proportions which are due to shared environment or unshared environment. While nearly all research is carried out using SEM
programs such as the freeware Mx, the essential logic of the twin design is as follows:
Monozygotic (MZ) twins raised in a family share both 100% of their genes, and all of the shared environment. Any differences arising between them in these circumstances are random (unique). The correlation we observe between MZ twins provides an estimate of A + C . Dizygous (DZ) twins have a common shared environment, and share on average 50% of their genes: so the correlation between DZ twins is a direct estimate of ½A + C . If r is the correlation observed for a particular trait, then:
Where rmz and rdz are simply the correlations of the trait in MZ and DZ twins respectively.
Twice difference between MZ and DZ twins gives us A: the additive genetic effect (Falconer's formula
). C is simply the MZ correlation minus our estimate of A. The random (unique) factor E is estimated directly by how much the MZ twin correlation deviates from 1. (Jinks & Fulker, 1970; Plomin, DeFries , McClearn, & McGuffin, 2001).
The difference between these two sums, then, allows us to solve for A, C, and E. As the difference between the MZ and DZ correlations is due entirely to a halving of the genetic similarity, the additive genetic effect 'A' is simply twice the difference between the MZ and DZ correlations:
As the MZ correlation reflects the full effect of A and C, E can be estimated by subtracting this correlation from 1
Finally, C can be derived:
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) is shown below:
Figure Caption: Danish male data (a representative population of eight independent multinational cohorts reported in Silventoinen et al. (2003)
This model shows the raw variance in height. That can be useful. Often, though, it renders a model more comprehensible to standardize the parameters. 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., standardized A = A/(A+C+E):
A principle 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, and also drop or add paths. Thus, for instance an AE model can be objectively compared to a full ACE model, to test for effect of family or shared environment on behavior. Thus we can ask of the figure above: Can C be dropped? Alternatively, confidence intervals can be calculated for each path.
Modeling also allows multivariate modeling: This is invaluable in answering questions about the genetic relationship between apparently different variables: 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).
Modeling tools such as OpenMx
and other applications suited to constraints and multiple groups have made the new techniques accessible to reasonably skilled users.
, and then contrive to make their IQs identical? Indeed, how could they?
This assumption, however, has been directly tested. An interesting case occurs where parents believe their twins to be non-identical when in fact they are genetically MZ. Studies of a range of psychological traits indicate that these children remain as concordant as MZs raised by parents who treated them as identical (Kendler, Neale, Kessler, Heath, & Eaves, 1993).
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. Addressing this limit requires incorporating adoption models, or children-of-twins designs, to assess family influences uncorrelated with shared genetic effects.
, statistics, and psychology
, with some arguing that conclusions reached via this method are ambiguous or meaningless. Core elements of these criticisms and their rejoinders are listed below.
Twin studies were found to be especially useful by the Third Reich. "... twin research was the clear means of choice for eugenically oriented human geneticists, stated in slightly exaggerated terms, precisely because of its theoretical weaknesses and sources of practical error - the heritability of those pathological phenomena at the focus of biopolitical interest could be proven more or less at will. [...] characterizes twin research as a pseudoscience."
estimates used for most twin studies rest on restrictive assumptions which are usually not tested, and if they are, can often found to be violated by the data.
For example, Peter Schonemann
has 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), the narrow heritability’s of HR 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
are not subject to the limitations and heritability estimates such as those noted above are mathematically impossible
. Critically, the newer methods allow for explicit testing of the role of different pathways and incorporation and testing of complex effects
.
of the population, and they differ in their developmental environment. In this sense they are not representative.
For example: Dizygotic (DZ) twin births are affected by many factors. Some women frequently produce more than one egg
at each menstrual period and, therefore, are more likely to have twins. This tendency may run in the family
either in the mother's or father's side of the family, 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 DZ and MZ twins
.
where the effects of experimentally randomized genotypes and environment combinations are measured. In human studies, we observe rather than control the exposure of individuals to different environments. Thus norms of reaction
can not be evaluated.
and its inherent confounding of causes is common in psychology. An inherent appeal of the classic twin design is that it begins to untangle these confounds. For example, in MZ and DZ twins shared environment and genetic effects are not confounded, as they are in non-twin familial studies. 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 argued to be a considerable advance over the alternative, which is no knowledge of the different roles of genes and environment whatsoever. 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.
No single design can address all issues. Additional information is available outside the classic twin design. Adoption designs are a form of natural experiment which tests norms of reaction by placing the same genotype in different environments. Association studies, e.g., 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, e.g.
Example: We can imagine that only males have voting rights (or another gender difference). The correlation for MZ twins is perfect (males have same rights and females have also same rights) but the correlation for all DZ twins (same sex male, same sex female and opposite sex) is less than perfect (males vs. females have different rights) i.e.
And the result can be misinterpreted that voting rights are heritable due to genetics. The correct interpretation of result is that rights correlate with sex. Note that correlation is symmetric and thus "correlation does not imply causation
". The evaluation of their parent traits and corresponding conditional probability
are necessary to estimate heritability.
Also, it should be noted that correlation is not causation, and that a t-Test is also a measure of correlation. Modern twin modelling goes well beyond correlations. Multivariate, and multiple-time wave studies, with measured environment and repeated measures of purported causal and consequential behaviours are now the norm. Examples of these models include extended twin designs, simplex models, and growth-curve models.
A second effect is "GE correlation", in which certain allelles occur more frequently than others in certain environments. If a gene causes a person to enjoy reading, then children with this allele are likely to be raised in households with books in them (due to GE correlation: one or both of their parents has the allele and therefore both accumulates a book collection and passes on the book-reading allele). Such effects can be assessed 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
as well as intelligence. 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.
al studies compare the agreement in continuously varying traits across twins.
For example, a group of 10 twins have been pre-selected to have one affected member (of the pair). During the course of the study four other previously non-affected members become affected, giving a pairwise concordance of 4/(4+6) or 4/10 or 40%.
For example, consider a group of 10 twins that have been pre-selected to have one affected member. During the course of the study, four other previously non-affected members become affected, giving a probandwise concordance of 8/(8+6) or 8/14 or 57%.
And in reply to this article see:
http://www.bga.org/, the International Society for Twin Studies, and the International Behavioural and Neural Genetics Society http://www.ibangs.org/. Behavior genetic work also features prominently in several more general societies, for instance the International Society of Psychiatric Genetics. http://www.ispg.net/.
, Genes, Brain and Behavior
, and Twin Research and Human Genetics.
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
influences on individual traits and behaviors. Twin research is considered a key tool in behavioral genetics and related fields. Alternate groups that can also be studied based on facts about genetic similarity include full siblings in general and adoptees
Adoption
Adoption is a process whereby a person assumes the parenting for another and, in so doing, permanently transfers all rights and responsibilities from the original parent or parents...
.
Twins are a valuable source for observation due to their genotypes and family environments tending to be similar. More specifically, monozygotic (MZ) or "identical" twin
Twin
A twin is one of two offspring produced in the same pregnancy. Twins can either be monozygotic , meaning that they develop from one zygote that splits and forms two embryos, or dizygotic because they develop from two separate eggs that are fertilized by two separate sperm.In contrast, a fetus...
s, share nearly 100% of their genetic polymorphisms
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
, which means that most variation in pairs' traits (measured height, susceptibility to boredom, intelligence, depression, etc.) is due to their unique experiences. Dizygotic (DZ) or "fraternal" twins share only about 50% of their polymorphisms. DZ twins are helpful to study because they tend to share many aspects of their environment (e.g., uterine environment, parenting style, education, wealth, culture, community) by virtue of being born in the same time and place.
The classical twin design compares the similarity of MZ (identical) and DZ (fraternal) twins. MZ twins are almost always more similar than DZ twins due to higher genetic similarity coupled with the same amount of environmental similarity. By comparing many hundreds of families of twins, researchers can then understand more about the complementary roles of genetic effects, shared environment, and unique environment in shaping people.
Modern twin studies have shown that almost all traits are in part influenced by genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
differences, with some characteristics showing a strong influence (e.g. height
Human height
Human height is the distance from the bottom of the feet to the top of the head in a human body standing erect.When populations share genetic background and environmental factors, average height is frequently characteristic within the group...
), others an intermediate level (e.g. intelligence quotient) and some more complex heritabilities
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...
, with evidence for different genes affecting different aspects of the trait - as in the case of autism
Heritability of autism
The heritability of autism is the proportion of autism that can be explained by genetic variation; if the heritability of a condition is high, then the condition is considered to be primarily genetic...
.
History
TWINS
Two Wide-Angle Imaging Neutral-Atom Spectrometers are a pair of NASA instruments aboard two United States National Reconnaissance Office satellites in Molniya orbits. TWINS was designed to provide stereo images of the Earth's ring current. The first instrument, TWINS-1, was launched aboard USA-184...
have been of interest to scholars since early civilization, such as the early physician Hippocrates
Hippocrates
Hippocrates of Cos or Hippokrates of Kos was an ancient Greek physician of the Age of Pericles , and is considered one of the most outstanding figures in the history of medicine...
(5th c. BCE
Common Era
Common Era ,abbreviated as CE, is an alternative designation for the calendar era originally introduced by Dionysius Exiguus in the 6th century, traditionally identified with Anno Domini .Dates before the year 1 CE are indicated by the usage of BCE, short for Before the Common Era Common Era...
), who attributed similar diseases in twins to shared material circumstances , and the stoic philosopher Posidonius
Posidonius
Posidonius "of Apameia" or "of Rhodes" , was a Greek Stoic philosopher, politician, astronomer, geographer, historian and teacher native to Apamea, Syria. He was acclaimed as the greatest polymath of his age...
(1st c. BCE), who attributed such similarities to shared astrological circumstances , the modern history of the twin study derives from Sir Francis Galton's pioneering use of twins to study the role of genes and environment on human development
Human development (biology)
Human development is the process of growing to maturity. In biological terms, this entails growth from a one-celled zygote to an adult human being.- Biological development:...
and behavior. Galton, however, was unaware of the critical genetic difference between MZ and DZ twins.
This factor was still not understood when the first study using psychological tests was conducted by Edward Thorndike
Edward Thorndike
Edward Lee "Ted" Thorndike was an American psychologist who spent nearly his entire career at Teachers College, Columbia University. His work on animal behavior and the learning process led to the theory of connectionism and helped lay the scientific foundation for modern educational psychology...
(1905) using 50-pairs of twin. Notably this paper was perhaps the first statement of the idea (formulated as a testable hypothesis) that C (family effects) decline with age: comparing 9-10 and 13-14 year old twin-pairs, and normal siblings born within a few years of one another.
Fatefully, however, Thorndike incorrectly reasoned that his data gave support for there being one, not two types of twins: Missing the critical distinction that makes within-family twin studies such a powerful resource in psychology and medicine. This mistake was repeated by Ronald Fisher
Ronald Fisher
Sir Ronald Aylmer Fisher FRS was an English statistician, evolutionary biologist, eugenicist and geneticist. Among other things, Fisher is well known for his contributions to statistics by creating Fisher's exact test and Fisher's equation...
(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.".
The first published twin study utilizing the distinction between MZ and DZ twins is sometimes cited as that of the German
Germans
The Germans are a Germanic ethnic group native to Central Europe. The English term Germans has referred to the German-speaking population of the Holy Roman Empire since the Late Middle Ages....
geneticist Hermann Werner Siemens
Hermann Werner Siemens
Hermann Werner Siemens was a German dermatologist who first described many skin diseases and was one of the inventors of the twin study.-Biography:...
in 1924. Chief among Siemens' innovations was the "polysymptomatic similarity diagnosis". This allowed him to overcome the barrier that had stumped Fisher and was a staple in twin research prior to the advent of molecular markers. Wilhelm Weinberg
Wilhelm Weinberg
Dr Wilhelm Weinberg was a German half-Jewish physician and obstetrician-gynecologist, practicing in Stuttgart, who in a 1908 paper Dr Wilhelm Weinberg (Stuttgart, December 25, 1862 – Tübingen, November 27, 1937) was a German half-Jewish physician and obstetrician-gynecologist, practicing in...
, however, had already by 1910 used the MZ-DZ distinction to calculate their respective rates from the ratios of same- and opposite-sex twins in a maternity population, worked out partitioning of covariation amongst relatives into genetic and environmental elements (anticipating Fisher
Ronald Fisher
Sir Ronald Aylmer Fisher FRS was an English statistician, evolutionary biologist, eugenicist and geneticist. Among other things, Fisher is well known for his contributions to statistics by creating Fisher's exact test and Fisher's equation...
and Wright
Sewall Wright
Sewall Green Wright was an American geneticist known for his influential work on evolutionary theory and also for his work on path analysis. With R. A. Fisher and J.B.S. Haldane, he was a founder of theoretical population genetics. He is the discoverer of the inbreeding coefficient and of...
) including the effect of dominance on relative's similarity, and begun the first classic-twin studies.
Methods
The power of twin designs arises from the fact that twins may be either monozygotic (MZ: developing from a single fertilized egg and therefore sharing all of their alleleAllele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s) – or dizygotic (DZ: developing from two fertilized eggs and therefore sharing on average 50% of their polymorphic
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
alleles, the same level of genetic similarity as found in non-twin siblings). These known differences in genetic similarity, together with a testable assumption of equal environments for MZ and DZ twins (Bouchard & Propping, 1993) creates the basis for the twin design for exploring the effects of genetic and environmental variance on a phenotype (Neale & Cardon, 1992).
The basic logic of the twin study can be understood with very little mathematics beyond an understanding of correlation
Correlation
In statistics, dependence refers to any statistical relationship between two random variables or two sets of data. Correlation refers to any of a broad class of statistical relationships involving dependence....
and the concept of variance
Variance
In probability theory and statistics, the variance is a measure of how far a set of numbers is spread out. It is one of several descriptors of a probability distribution, describing how far the numbers lie from the mean . In particular, the variance is one of the moments of a distribution...
.
Like all behavior genetic research, the classic twin study begins from assessing the variance of a behavior (called a phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
by geneticists) in a large group, and attempts to estimate how much of this is due to genetic effects (heritability
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...
), and how much appears to be due to shared or unique environmental effects - events that affect each twin in a different way, or events that occur to one twin but not another.
Typically these three components are called A (additive genetics) C (common environment) and E (unique environment); the so-called ACE Model. It is also possible to examine non-additive genetics effects (often denoted D for dominance (ADE model
ADE model
An ADE model is a genetic model for twin studies which includes dominance genetic effects.. Biometrical genetic modeling of twin or other family data can be used to decompose the variance of an observed response or phenotype into genetic and environmental components...
); see below for more complex twin designs).
Given the ACE model, researchers can determine what proportion of variance in a trait is heritable, versus the proportions which are due to shared environment or unshared environment. While nearly all research is carried out using SEM
Structural equation modeling
Structural equation modeling is a statistical technique for testing and estimating causal relations using a combination of statistical data and qualitative causal assumptions...
programs such as the freeware Mx, the essential logic of the twin design is as follows:
Monozygotic (MZ) twins raised in a family share both 100% of their genes, and all of the shared environment. Any differences arising between them in these circumstances are random (unique). The correlation we observe between MZ twins provides an estimate of A + C . Dizygous (DZ) twins have a common shared environment, and share on average 50% of their genes: so the correlation between DZ twins is a direct estimate of ½A + C . If r is the correlation observed for a particular trait, then:
- rmz = A + C
- rdz = ½A + C
Where rmz and rdz are simply the correlations of the trait in MZ and DZ twins respectively.
Twice difference between MZ and DZ twins gives us A: the additive genetic effect (Falconer's formula
Falconer's formula
Falconer's formula is used in twin studies to determine the genetic heritability of a trait based on the difference between twin correlations.The formula is hb2 = 2, where hb2 is the broad sense heritability, rmz is the identical twin correlation, and rdz is the fraternal twin correlation...
). C is simply the MZ correlation minus our estimate of A. The random (unique) factor E is estimated directly by how much the MZ twin correlation deviates from 1. (Jinks & Fulker, 1970; Plomin, DeFries , McClearn, & McGuffin, 2001).
The difference between these two sums, then, allows us to solve for A, C, and E. As the difference between the MZ and DZ correlations is due entirely to a halving of the genetic similarity, the additive genetic effect 'A' is simply twice the difference between the MZ and DZ correlations:
- A = 2 (rmz – rdz)
As the MZ correlation reflects the full effect of A and C, E can be estimated by subtracting this correlation from 1
- E = 1 – rmz
Finally, C can be derived:
- C = rmz – A = 2 rdz – rmz
Modern Modeling
Beginning in the 1970s, research transitioned to modelingStructural equation modeling
Structural equation modeling is a statistical technique for testing and estimating causal relations using a combination of statistical data and qualitative causal assumptions...
genetic, environmental effects using maximum likelihood
Maximum likelihood
In statistics, maximum-likelihood estimation is a method of estimating the parameters of a statistical model. When applied to a data set and given a statistical model, maximum-likelihood estimation provides estimates for the model's parameters....
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) is shown below:
Figure Caption: Danish male data (a representative population of eight independent multinational cohorts reported in Silventoinen et al. (2003)
This model shows the raw variance in height. That can be useful. Often, though, it renders a model more comprehensible to standardize the parameters. 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., standardized A = A/(A+C+E):
A principle 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, and also drop or add paths. Thus, for instance an AE model can be objectively compared to a full ACE model, to test for effect of family or shared environment on behavior. Thus we can ask of the figure above: Can C be dropped? Alternatively, confidence intervals can be calculated for each path.
Modeling also allows multivariate modeling: This is invaluable in answering questions about the genetic relationship between apparently different variables: 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).
Modeling tools such as OpenMx
OpenMx
OpenMx is an open source program for extended structural equation modeling. It runs as a package under R. Cross platform, it runs under Linux, Mac OS and Windows....
and other applications suited to constraints and multiple groups have made the new techniques accessible to reasonably skilled users.
Assumptions
It can be seen from the modelling above, that the main assumption of the twin study is that of equal environments. At an intuitive level, this seems reasonable – why would parents note that two children shared their hair and eye colorEye color
Eye color is a polygenic phenotypic character and is determined by two distinct factors: the pigmentation of the eye's iris and the frequency-dependence of the scattering of light by the turbid medium in the stroma of the iris....
, and then contrive to make their IQs identical? Indeed, how could they?
This assumption, however, has been directly tested. An interesting case occurs where parents believe their twins to be non-identical when in fact they are genetically MZ. Studies of a range of psychological traits indicate that these children remain as concordant as MZs raised by parents who treated them as identical (Kendler, Neale, Kessler, Heath, & Eaves, 1993).
Measured similarity: A direct test of assumptions in twin designs
A particularly powerful technique for testing the twin method has recently been reported by Visscher et al. 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.Extended twin designs and more complex genetic models
The basic or classical twin-design contains only MZ and DZ 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
Gene-environment correlation
Gene-environment correlation is said to occur when exposure to environmental conditions depends on an individual's genotype.-Definition:...
and interaction
Gene-environment interaction
Gene–environment interaction is the phenotypic effect of interactions between genes and the environment....
, as well as other non-additive effects on behavior. The revolution in molecular genetics
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
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. Addressing this limit requires incorporating adoption models, or children-of-twins designs, to assess family influences uncorrelated with shared genetic effects.
Criticism
The Twin Method has been subject to criticism from statistical geneticsGenetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, statistics, and psychology
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...
, with some arguing that conclusions reached via this method are ambiguous or meaningless. Core elements of these criticisms and their rejoinders are listed below.
Twin studies were found to be especially useful by the Third Reich. "... twin research was the clear means of choice for eugenically oriented human geneticists, stated in slightly exaggerated terms, precisely because of its theoretical weaknesses and sources of practical error - the heritability of those pathological phenomena at the focus of biopolitical interest could be proven more or less at will. [...] characterizes twin research as a pseudoscience."
Criticisms of Statistical Methods
It has been argued that the statistical underpinnings of twin research are invalid. Such statistical critiques argue that heritabilityHeritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...
estimates used for most twin studies rest on restrictive assumptions which are usually not tested, and if they are, can often found to be violated by the data.
For example, Peter Schonemann
Peter Schonemann
Peter H. Schönemann was a German born psychometrician and statistical expert. He was Professor Emeritus in the Department of Psychological Sciences at Purdue University. His research interests included multivariate statistics, multidimensional scaling and measurement, quantitative behavior...
has criticized methods for estimating heritability
Heritability
The Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...
developed in the 1970s. He has also argued that the heritability estimate from a twin study may reflect factors other than shared genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
. Using the statistical models published in Loehlin
John C. Loehlin
John Clinton Loehlin is an American behavior geneticist and psychology and computer science professor emeritus. Loehlin has served as president of the Behavior Genetics Association and of the Society for Multivariate Experimental Psychology....
and Nichols (1976), the narrow heritability’s of HR 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
Responses to Statistical Critiques
In the days before the computer, statisticians were forced to use methods which 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 modelingStructural equation modeling
Structural equation modeling is a statistical technique for testing and estimating causal relations using a combination of statistical data and qualitative causal assumptions...
are not subject to the limitations and heritability estimates such as those noted above are mathematically impossible
. Critically, the newer methods allow for explicit testing of the role of different pathways and incorporation and testing of complex effects
.
Sampling: Twins as representative members of the population
The results of twin studies cannot be automatically generalized beyond the population in which they have been derived. It is therefore important to understand the particular sample studied, and the nature of twins themselves. Twins are not a random sampleRandom sample
In statistics, a sample is a subject chosen from a population for investigation; a random sample is one chosen by a method involving an unpredictable component...
of the population, and they differ in their developmental environment. In this sense they are not representative.
For example: Dizygotic (DZ) twin births are affected by many factors. Some women frequently produce more than one egg
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
at each menstrual period and, therefore, are more likely to have twins. This tendency may run in the family
Family
In human context, a family is a group of people affiliated by consanguinity, affinity, or co-residence. In most societies it is the principal institution for the socialization of children...
either in the mother's or father's side of the family, 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
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
and in vitro fertilization-embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
replacement can also give rise to DZ and MZ twins
.
Response to representativeness of twins
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).Observational nature of twin studies
For very obvious reasons, studies of twins are with almost no exceptions observational. This contrasts with, for instance, studies in plants or in animal breedingAnimal breeding
Animal breeding is a branch of animal science that addresses the evaluation of the genetic value of domestic livestock...
where the effects of experimentally randomized genotypes and environment combinations are measured. In human studies, we observe rather than control the exposure of individuals to different environments. Thus norms of reaction
Norms of reaction
In ecology and genetics, a norm of reaction describes the pattern of phenotypic expression of a single genotype across a range of environments. One use of norms of reaction is in describing how different species—especially related species—respond to varying environments...
can not be evaluated.
Response to Observational criticism
The observational studyObservational study
In epidemiology and statistics, an observational study draws inferences about the possible effect of a treatment on subjects, where the assignment of subjects into a treated group versus a control group is outside the control of the investigator...
and its inherent confounding of causes is common in psychology. An inherent appeal of the classic twin design is that it begins to untangle these confounds. For example, in MZ and DZ twins shared environment and genetic effects are not confounded, as they are in non-twin familial studies. 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 argued to be a considerable advance over the alternative, which is no knowledge of the different roles of genes and environment whatsoever. 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.
No single design can address all issues. Additional information is available outside the classic twin design. Adoption designs are a form of natural experiment which tests norms of reaction by placing the same genotype in different environments. Association studies, e.g., allow direct study of allelic effects. Mendelian Randomization
Mendelian randomization
In epidemiology, Mendelian randomization is a method of using measured variation in genes of known function to examine the causal effect of a modifiable exposure on disease in non-experimental studies...
of alleles also provides opportunities to study the effects of Alleles at random with respect to their associated environments and other genes, e.g.
Criticisms of correlation model
An enormous complexity exists in the interrelationships between genetic and environmental factors in determining traits. All their correlations can not be known and experiments can not be evaluated without specifying related allele(s). DZ twins with differences in other alleles must be excluded from calculations.Example: We can imagine that only males have voting rights (or another gender difference). The correlation for MZ twins is perfect (males have same rights and females have also same rights) but the correlation for all DZ twins (same sex male, same sex female and opposite sex) is less than perfect (males vs. females have different rights) i.e.
- rmz = 1
- rdz < 1
And the result can be misinterpreted that voting rights are heritable due to genetics. The correct interpretation of result is that rights correlate with sex. Note that correlation is symmetric and thus "correlation does not imply causation
Correlation does not imply causation
"Correlation does not imply causation" is a phrase used in science and statistics to emphasize that correlation between two variables does not automatically imply that one causes the other "Correlation does not imply causation" (related to "ignoring a common cause" and questionable cause) is a...
". The evaluation of their parent traits and corresponding conditional probability
Conditional probability
In probability theory, the "conditional probability of A given B" is the probability of A if B is known to occur. It is commonly notated P, and sometimes P_B. P can be visualised as the probability of event A when the sample space is restricted to event B...
are necessary to estimate heritability.
Response to correlation criticism
Modern twin modeling rarely pools the three types of DZ twins into one group. A standard analysis would test for sex-limitation by fitting models to five groups, MZ male, MZ female, DZ male, DZ female, and DZ opposite sex. In this example the five correlations would be 1, 1, 1, 1, and -1. Modeling results would indicate that shared environment factors cause variation in each sex, but that they act in opposite directions (correlate negative one) in males and females. These results would be entirely consistent with the sources of variation for this trait in this culture.Also, it should be noted that correlation is not causation, and that a t-Test is also a measure of correlation. Modern twin modelling goes well beyond correlations. Multivariate, and multiple-time wave studies, with measured environment and repeated measures of purported causal and consequential behaviours are now the norm. Examples of these models include extended twin designs, simplex models, and growth-curve models.
Interactions
The effects of genes depend on the environment they are in. Possible complex genetic effects include 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 (in this case the slope of response to an environment would differ between genotypes).A second effect is "GE correlation", in which certain allelles occur more frequently than others in certain environments. If a gene causes a person to enjoy reading, then children with this allele are likely to be raised in households with books in them (due to GE correlation: one or both of their parents has the allele and therefore both accumulates a book collection and passes on the book-reading allele). Such effects can be assessed 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
Compulsory education
Compulsory education refers to a period of education that is required of all persons.-Antiquity to Medieval Era:Although Plato's The Republic is credited with having popularized the concept of compulsory education in Western intellectual thought, every parent in Judea since Moses's Covenant with...
begins. This is observed for instance in reading
as well as intelligence. 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.
Continuous variable or Correlational studies
While concordance studies compare traits which are either present or absent in each twin, correlationCorrelation
In statistics, dependence refers to any statistical relationship between two random variables or two sets of data. Correlation refers to any of a broad class of statistical relationships involving dependence....
al studies compare the agreement in continuously varying traits across twins.
Pairwise concordance
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.For example, a group of 10 twins have been pre-selected to have one affected member (of the pair). During the course of the study four other previously non-affected members become affected, giving a pairwise concordance of 4/(4+6) or 4/10 or 40%.
Probandwise concordance
For a group of twins in which at least one member of each pair is affected, probandwise concordance is a measure of the proportion of twins who have the illness who have an affected twin and can be calculated with the formula of 2C/(2C+D), in which C is the number of concordant pairs and D is the number of discordant pairs.For example, consider a group of 10 twins that have been pre-selected to have one affected member. During the course of the study, four other previously non-affected members become affected, giving a probandwise concordance of 8/(8+6) or 8/14 or 57%.
See also
- Behavioral genetics
- The "Burt Affair"
- Gene-environment interactionGene-environment interactionGene–environment interaction is the phenotypic effect of interactions between genes and the environment....
- Gene-environment correlationGene-environment correlationGene-environment correlation is said to occur when exposure to environmental conditions depends on an individual's genotype.-Definition:...
- HeritabilityHeritabilityThe Heritability of a population is the proportion of observable differences between individuals that is due to genetic differences. Factors including genetics, environment and random chance can all contribute to the variation between individuals in their observable characteristics...
- Heritability of IQ
- Human natureHuman natureHuman nature refers to the distinguishing characteristics, including ways of thinking, feeling and acting, that humans tend to have naturally....
- Identical Strangers: A Memoir of Twins Separated and ReunitedIdentical StrangersIdentical Strangers: A Memoir of Twins Separated and Reunited is a 2007 memoir written by Elyse Schein and Paula Bernstein and published by Random House. The twins were given up by their mentally ill mother and separated as infants, in part, to participate in a twin study. They were adopted by...
- Kaiser Wilhelm Institute of Anthropology, Human Heredity, and EugenicsKaiser Wilhelm Institute of Anthropology, Human Heredity, and EugenicsThe Kaiser Wilhelm Institute of Anthropology, Human Heredity, and Eugenics was founded in 1927. The Rockefeller Foundation supported both the Kaiser Wilhelm Institute of Psychiatry and the Kaiser Wilhelm Institute of Anthropology, Human Heredity and Eugenics...
- Nature versus nurtureNature versus nurtureThe nature versus nurture debate concerns the relative importance of an individual's innate qualities versus personal experiences The nature versus nurture debate concerns the relative importance of an individual's innate qualities ("nature," i.e. nativism, or innatism) versus personal experiences...
- Otmar Freiherr von VerschuerOtmar Freiherr von VerschuerOtmar Freiherr von Verschuer was a German human biologist and eugenicist concerned primarily with "racial hygiene" and twin research...
- Quantitative geneticsQuantitative geneticsQuantitative genetics is the study of continuous traits and their underlying mechanisms. It is effectively an extension of simple Mendelian inheritance in that the combined effects of one or more genes and the environments in which they are expressed give rise to continuous distributions of...
- Differential SusceptibilityDifferential susceptibility hypothesisAccording to the differential susceptibility hypothesis by Belsky individuals vary in the degree they are affected by experiences or qualities of the environment they are exposed to...
Further reading
- Textbook, software, and example scripts for twin research
- Jang, K.L., McCrae, R.R., Angleitner, A. Riemann, R. & Livesley, W.J. (1998). Heritability of facet-level traits in a cross-cultural twin sample: support for a hierarchical modelHierarchical modelA hierarchical database model is a data model in which the data is organized into a tree-like structure. The structure allows representing information using parent/child relationships: each parent can have many children, but each child has only one parent...
of personality. Journal of Personality and Social Psychology 74:1556-1565. - Plomin, DeFries, McClearn & McGuffin (2000). Behavioral Genetics: A Primer 4th edition. W.H.Freeman & Co Ltd.
- Nancy L. Segal (2005) Indivisible by Two: Lives of Extraordinary Twins. New York, Harvard University PressHarvard University PressHarvard University Press is a publishing house established on January 13, 1913, as a division of Harvard University, and focused on academic publishing. In 2005, it published 220 new titles. It is a member of the Association of American University Presses. Its current director is William P...
. - Am J Med Genet C Semin Med Genet. 2009 May 15;151C(2):136-41. Not really identical: epigenetic differences in monozygotic twins and implications for twin studies in psychiatry. Haque FN, Gottesman II, Wong AH.
Critical accounts
- Peter SchonemannPeter SchonemannPeter H. Schönemann was a German born psychometrician and statistical expert. He was Professor Emeritus in the Department of Psychological Sciences at Purdue University. His research interests included multivariate statistics, multidimensional scaling and measurement, quantitative behavior...
(1997). Models and muddles of heritability. Genetica, 99, 97-108: http://www2.psych.purdue.edu/~phs/pdf/81.pdf - Peter SchonemannPeter SchonemannPeter H. Schönemann was a German born psychometrician and statistical expert. He was Professor Emeritus in the Department of Psychological Sciences at Purdue University. His research interests included multivariate statistics, multidimensional scaling and measurement, quantitative behavior...
and Roberta D. Schonemann (1994). Environmental versus genetic models for Osborne’s personality data on identical and fraternal twins. CPC, 1994, 13 (2), 141-167 http://www2.psych.purdue.edu/~phs/pdf/71.pdf - Kamin, L. J. (1974). The Science and Politics of I.Q. Potomac, MD: Lawrence Erlbaum Associates.
- Kempthorne O. (1997). Heritability: uses and abuses. Genetica, Volume 99, Numbers 2-3, 1997 , pp. 109–112(4)
- Joseph, J. (2003). The Gene Illusion: Genetic Research in Psychiatry and Psychology Under the Microscope.The Gene IllusionThe Gene Illusion is a book by clinical psychologist Jay Joseph, published in 2003, which challenges the evidence underlying genetic theories in psychiatry and psychology. Focusing primarily on twin and adoption studies, he attempts to debunk the methodologies used to establish genetic...
PCCS Books.
- This book has been critically reviewed for the American Psychological Association. Hanson, D. R. (2005). 'The Gene Illusion Confusion: A review of The Gene Illusion: Genetic Research in Psychiatry and Psychology Under the Microscope by Jay Joseph' [Electronic Version]. PsycCritiques, 50, e14.
- Christiane Capron, Adrian R. Vetta, Michel Duyme and Atam Vetta (1999). Misconceptions of biometrical IQists. Cahiers de Psychologie Cognitive/Current Psychology of Cognition 1999, 18 (2), 115-160
- Horwitz AV, Videon TM, Schmitz MF, Davis D. Rethinking twins and environments: possible social sources for assumed genetic influences in twin research. J Health Soc Behav. 2003 Jun;44(2):111-129.
And in reply to this article see:
- Freese J and Powell B Tilting at Twindmills: rethinking sociological responses to behavioral genetics. J Health Soc Behav. 2003 Jun;44(2):130-135.
Academic bodies
Several academic bodies exist to support behavior genetic research, including the Behavior Genetics AssociationBehavior Genetics Association
The Behavior Genetics Association is a learned society that was established in 1970 and promotes research into the connection between heredity and behavior.- Aims :...
http://www.bga.org/, the International Society for Twin Studies, and the International Behavioural and Neural Genetics Society http://www.ibangs.org/. Behavior genetic work also features prominently in several more general societies, for instance the International Society of Psychiatric Genetics. http://www.ispg.net/.
Journals
Prominent specialist journals in the field include Behavior GeneticsBehavior Genetics (journal)
Behavior Genetics is a peer-reviewed scientific journal published monthly by Springer Science+Business Media that is devoted to "research in the inheritance of behavior". It is the official journal of the Behavior Genetics Association. The journal was founded in 1971 with Steven G. Vandenberg as...
, Genes, Brain and Behavior
Genes, Brain and Behavior
According to the Journal Citation Reports, its 2009 impact factor is 4.061, ranking Genes, Brain and Behavior 63rd out of 237 listed journals in the category "Neurosciences" and 6th out of 48 listed journals in the category "Behavioral Sciences"....
, and Twin Research and Human Genetics.
Studies
The following Twin Studies are ongoing studies that are recruiting subjects:- Maudsley Bipolar Twin StudyMaudsley Bipolar Twin StudyThe Maudsley Bipolar Twin Study is an ongoing twin study of bipolar disorder running at the Institute of Psychiatry, London since 2003. The study is investigating possible differences between people with a diagnosis of bipolar disorder and people without the diagnosis...
, London, UKLondonLondon is the capital city of :England and the :United Kingdom, the largest metropolitan area in the United Kingdom, and the largest urban zone in the European Union by most measures. Located on the River Thames, London has been a major settlement for two millennia, its history going back to its...
(Home page) - Queensland Institute for Medical Research, Genetic Epidemiology Laboratory
- The Twin Research Unit (King's College London) UK
- The East Flanders Prospective Twin Survey
- University of Pennsylvania Sleep Research Study for Twins
- The Birmingham Registry for Twin and Heritability Studies
- The Twins and Multiple Births Association heritability study
- The Wisconsin Twin Research Project