Collections of twins are the closest that researchers can get in humans to an ideal study situation in which a large number of genetically identical individuals follow the same life courses. Comparison studies with as many factors as possible made the same are a good way to tease out relevant details from an exceedingly complex system that is still poorly understood as a whole. That system here is the sum total of human cell and tissue biology, and its changing operation over the course of a life span: the map of metabolism is at present really only a sketch of the outlines, and contains many large blank areas when it comes to the precise details. An example of the use of twin studies is to identify twin pairs where one has a medical condition and the other does not (a set of "disease-discordant" twins), a situation that should make it much easier to identify important differences and thus more quickly identify the most relevant biochemical mechanisms involved in the development and progression of that medical condition.
Monozygotic (MZ) twins share nearly all of their genetic variants and many similar environments before and after birth. However, they can also show phenotypic discordance for a wide range of traits. Differences at the epigenetic level may account for such discordances. It is well established that epigenetic states can contribute to phenotypic variation, including disease. Epigenetic states are dynamic and potentially reversible marks involved in gene regulation, which can be influenced by genetics, environment, and stochastic events. Here, we review advances in epigenetic studies of discordant MZ twins, focusing on disease.
The study of epigenetics and disease using discordant MZ twins offers the opportunity to control for many potential confounders encountered in general population studies, such as differences in genetic background, early-life environmental exposure, age, gender, and cohort effects. Recently, analysis of disease-discordant MZ twins has been successfully used to study epigenetic mechanisms in aging, cancer, autoimmune disease, psychiatric, neurological, and multiple other traits. Epigenetic aberrations have been found in a range of phenotypes, and challenges have been identified, including sampling time, tissue specificity, validation, and replication. The results have relevance for personalized medicine approaches, including the identification of prognostic, diagnostic, and therapeutic targets. The findings also help to identify epigenetic markers of environmental risk and molecular mechanisms involved in disease and disease progression, which have implications both for understanding disease and for future medical research.