Twin studies

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Identical or monozygotic twins, by virtue of arising from the fertilization of one egg, share 100 per cent of their genes. Non-identical or dizygotic twins are from two fertilized eggs and like full biological siblings share on average 50 per cent of their genes. Thus, assuming that monozygotic twins and dizygotic twins share environment to the same extent, monozygotic twins would share greater similarity than dizygotic twins for a disorder that is genetically influenced. Twin studies are an important method for disentangling the effects of genes and shared environment and can be used to estimate the contribution of genetic influences, shared environmental factors and non-shared environmental factors to the total variation for a given trait or disorder.

For continuous traits, twin similarity is expressed as an intraclass correlation coefficient where:

Thus, from observed monozygotic and dizygotic correlations for a given trait we can calculate heritability from the above equations where h2 = 2(rmz - rdz), c2 = 2rdz -

rmz, and e2 is the remaining variance = 1 - h2 - c2 (see 2ath.aoaly.sis. below).

For dichotomous characteristics (e.g. affected with a disorder and unaffected), twin similarity is expressed as concordance rates. A pairwise concordance rate is estimated as the number of twin pairs who both have the disorder divided by the total number of pairs. However, where there has been systematic ascertainment, for example a twin register, it is preferable to report a probandwise concordance rate which is calculated as the number of affected twins divided by the total number of cotwins.

Ascertainment

One potential source of bias in twin studies stems from ascertainment procedures. For example, affected twins referred to a specific study or volunteer samples are likely to include more twin pairs who are monozygotic and who are concordant. Ascertainment of twin pairs through hospital registers overcomes this problem to some extent, but for some disorders may be biased by the process of referral. Population-based samples overcome these biases, although when examining disorders rather than traits extremely large sample sizes are required to obtain an adequate number of affected individuals.

Zygosity

A further potential source of error is in the assignment of zygosity. Ideally zygosity should be determined by DNA typing. However, it may be more practical to use a twin similarity questionnaire which includes questions such as whether the twins share the same hair/eye colour, and whether they look alike as two peas in a pod. This method of assigning zygosity is simple and inexpensive with a reported accuracy of over 90 per cent.

Equal environments assumption

It is sometimes argued that a major drawback to the twin study method is that monozygotic twins may experience a more similar environment and may be treated more similarly than dizygotic twins. However, where there is evidence that monozygotic twins share greater environmental similarity than dizygotic twins it is difficult to infer whether this contributes to their similarity for the disorder or whether this is the consequence of greater genetic similarity. There have been several approaches adopted to further explore this issue.

In some studies questionnaire measures of environmental sharing (e.g. being dressed alike as children, sharing friends) have been used. These suggest that environmental sharing is indeed greater for monozygotic twins than for dizygotic twins. However, it appears that for many traits and disorders such as cognitive ability, personality, depressive symptoms and depressive disorder this degree of similarity for childhood environment does not account for monozygotic twin similarity for the trait. One way of disentangling cause and effect is to use direct observational studies. Although this method has not been much used, one study of young twins suggested that the greater similarity of parental responses to monozygotic twins compared to dizygotic twins appeared to be elicited by the twins themselves.

An alternative method of examining the effects of environmental sharing is to study twins who are mistaken about their zygosity. However, most studies which have used this method suggest that perceived zygosity is a less important influence on twin similarity than true zygosity.

Finally, the most powerful means of examining the effects of environmental sharing is to look at monozygotic twins who have been reared apart. However, such twin pairs are rare and have mostly been ascertained in a biased fashion. Nevertheless, studies of reared-apart twins have informed us that there is a substantial genetic contribution to cognition, personality, and psychosis.

Comparability of twins

The final potential criticism of the twin method is whether twins can be regarded as representative of the general population given some important differences. Twin births are relatively common (1 in 80 births), although the number of dizygotic twins varies in different countries and is influenced by factors such as maternal age and multiparity, a family history of twins and increasingly, the use of fertility drugs. Twins are more likely to experience greater intrauterine and perinatal adversity and the experience of being brought up as a twin is unusual in itself. There is also some evidence that depression is more common in mothers of young twins than among mothers of singletons. However, these differences are only important if they result in different rates of disorder or symptoms in twins compared to singletons. So far there is little evidence to suggest that the rate of psychiatric disorder in twins is any higher than amongst singletons.

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