Twin studies in autoimmune disease: genetics, gender and environment

Twin studies are powerful tools to discriminate whether a complex disease is due to genetic or environmental factors. High concordance rates among monozygotic (MZ) twins support genetic factors being predominantly involved, whilst low rates are suggestive of environmental factors. Twin studies have often been utilised in the study of systemic and organ specific autoimmune diseases. As an example, type I diabetes mellitus has been investigated to establish that that disease is largely affected by genetic factors, compared to rheumatoid arthritis or scleroderma, which have a weaker genetic association. However, large twin studies are scarce or virtually non-existent in other autoimmune diseases which have been limited to few sets of twins and individual case reports. In addition to the study of the genetic and environmental contributions to disease, it is likely that twin studies will also provide data in regards to the clinical course of disease, as well as risk for development in related individuals. More importantly, genome-wide association studies have thus far reported genomic variants that only account for a minority of autoimmunity cases, and cannot explain disease discordance in MZ twins. Future research is therefore encouraged not only in the analysis of twins with autoimmune disease, but also in regards to epigenetic factors or rare variants that may be discovered with next-generation sequencing. This review will examine the literature surrounding twin studies in autoimmune disease including discussions of genetics and gender.