Twin-based DNA methylation analysis takes the center stage of studies of human complex diseases

The etiology of complex diseases is characterized by the interaction between the genome and environmental conditions and the interface of epigenetics may be a central mechanism. Current technologies already allow us high-throughput profiling of epigenetic patterns at genome level. However, our understanding of the epigenetic processes remains limited. Twins are special samples in genetic studies due to their genetic similarity and rearing-environment sharing. In the past decades, twins have made a great contribution in dissecting the genetic and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable samples of twins are helping to bridge the gap between gene activity and environmental conditions through epigenetic mechanisms unlimited to DNA sequence variations. We review the recent progresses in using twins to study disease-related molecular epigenetic phenotypes and link them with environmental exposures especially early life events. Various study designs and application issues will be highlighted and discussed with aim at making uses of twins in assessing the environmental impact on epigenetic changes during the development of complex diseases.