Common use of Assumptions and Limitations Clause in Contracts

Assumptions and Limitations. In order for a twin study to be valid, some key assumptions must be met. The most important and perhaps contentious being that to the extent that twins have a shared familial environment, MZ and DZ twins, on average, share their environments to the same degree. This is known as the equal environments assumption (EEA). This can be interpreted as both MZ and DZ twins are exposed to the same (often unknown) environmental factors that may contribute to the phenotypic variance. If MZ interact with their environment in a way that is more similar to the environmental interaction that DZ twins experience, then any estimate of the genetic effect on the phenotype being studied is likely to be inflated. Conversely, where the opposite is true, i.e. DZ twins systematically experience more similar environmental influences than MZ twins with respect to a specific phenotype, the genetic contribution will be underestimated. Violation of the EEA can occur at pre- and post-term – in utero monochorionic, monoamniotic MZ twins share the same placenta and amniotic sac. One argument is that the co-localisation of both MZ foetuses confers a more similar intrauterine environment than the majority of DZ twins, which do not share a placenta. Conversely, competition between monochorionic, monoamniotic MZ foetuses for resources may drive intrauterine differences such as those experienced in twin–twin transfusion syndrome (▇▇▇▇ et al., 2009). Differences in environmental interaction between MZ and DZ twin pairs may continue from childhood into adulthood, where perceived zygosity may influence behaviour and preferences. MZ and DZ twins may have identical or opposite, for example, dietary habits and physical activity levels as they or their parents (unconsciously) augment or lessen, similarity between them. Another assumption of the classical twin study is that the total observed phenotypic variance must be the same for MZ and DZ twins. Equal variances for MZ and DZ twins indicates the two groups represent a single homogenous group. Twins are assumed to be representative of the population from which they are sampled from, so that inferences made about the relative contributions to the phenotype can be generalised. In practical terms, this means for continuous phenotypes, such as height or weight, twins and randomly selected individuals from the population should have the same means and variances if the sample size collected is sufficiently large. Similarly, to make claims about a genetic contribution to a disease, the disease prevalence in the twin sample must be the same as in the population from which the twins are drawn from. Twin registries must ensure they do not have a bias in their recruitment such as advertising solely in hospitals, which artificially increases the prevalence of those diseases that require hospital treatment. Based upon the assumptions outlined above, twin studies allow empirical estimation of the genetic contribution to a phenotype by comparing concordance between MZ and DZ twins. As stated previously, MZ twins are formed by the cleavage of a single fertilised zygote into two separate zygotes, therefore are genetically identical, sharing additive and dominance variances completely. Whilst DZ twins result from the independent fertilisation of two eggs and share, on average, 50% of the alleles at all autosomal loci, making DZ twins no more genetically similar than any other full siblings.