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Twin studies are studies conducted on Identical twin or Fraternal twin twins. They aim to reveal the importance of environmental and genetics influences for traits, , 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 genotype: "identical" or monozygotic (MZ) 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.Plomin, R.; DeFries, J. C.; Knopik, V. S.; Neiderhiser, J. M. (Ed.). (2014). Behavioral Genetics (6th ed.). New York, NY: Worth Publishers "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 all 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 Phenotypic trait are partly influenced by Genetics differences, with some characteristics showing a stronger influence (e.g. Human height), others an intermediate level (e.g. personality traits) and some more complex heritability, with evidence for different genes affecting different aspects of the trait – as in the case of autism.
Gustav III, King of Sweden was the first to commission a medical study using identical twins. 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. Both Gustav III and his father had read and been strongly influenced by a 1715 treatise from a French people physician on the dangers of what would later be identified as caffeine in tea and coffee. 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.
A more recent study is from Galton 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 monozygotic and dizygotic twins. This factor was still not understood when the first study using psychological tests was conducted by Edward Thorndike (1905) using fifty pairs of twins. 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. laid the foundations of behavior genetics as a branch of science.]]
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
An early, and perhaps first, study understanding the distinction is from the Germans geneticist Hermann Werner Siemens in 1924. 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 Ronald Fisher and Sewall Wright, including the effect of dominance on similarity of relatives, and beginning the first classic-twin studies.
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."
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.
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 rmz and rdz 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 - rmz), i.e. MZ twins differ due to unique environments only (Jinks & Fulker, 1970; Plomin, DeFries, McClearn, & McGuffin, 2001).
An example structural model (for the heritability of height among Danish males) 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.
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, simplex models, and growth-curve models.
SEM programs such as OpenMx and other applications suited to constraints and multiple groups have made the new techniques accessible to reasonably skilled users.
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.
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).
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.
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. A 2016 study determined that the assumption that the prenatal environment of twins was equal was largely tenable.. Researchers continue to debate whether or not the equal environment assumption is valid.Fosse, Roar, Jay Joseph, and Ken Richardson. "A critical assessment of the equal-environment assumption of the twin method for schizophrenia." Frontiers in psychiatry 6 (2015): 62.Joseph, Jay. The trouble with twin studies: A reassessment of twin research in the social and behavioral sciences. Routledge, 2014.
In an extreme case, a gene may only be expressed in one sex (qualitative sex limitation). 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.
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
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.
revisited in:
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. 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.M. C. Neale and H. H. Maes. (1996). Methodology for genetics studies of twins and families. Journal. 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. Additional information is available outside the classic twin design. Adoption Study are a form of natural experiment that 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.
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.
For example: Dizygotic (DZ) twin births are affected by many factors. Some women frequently produce more than one ovum 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. (1983). 9780712602044, Century. ISBN 9780712602044
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%.
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