Epigenetics of Complex Diseases & Traits
Twin studies have shown the heritability of many complex diseases to be as high a 80%. However, the known associated sequence variants from genome-wide association studies (GWAS), and account for relatively small increase in disease risk and explain only a small proportion of familial clustering. This missing heritability from GWAS may in part be explained by the contribution of epigenetic variation to the complex phenotypes. Since environment contributes to phenotype in part through epigenetics, epigenetic marks can act as indicators of environmental effects. Moreover, epigenetic marks reactive to environment may serve as disease biomarkers or intervention targets.
The epigenetic status of a specific genomic region is determined by the sum of genetic and cumulative environmental and stochastic factors. Therefore, a within-pair comparison of discordant monozygotic (MZ) twin pairs is an ideal design for studying the contribution of epigenetic factors in complex diseases and traits.
Epigenetic studies of twins offer the advantage of allowing both a better understanding of the factors regulating epigenetic profiles, and of the role that epigenetic effects have in obesity. The inherent capacity to control for genetic variation in MZ twin pairs has proven incredibly valuable in studying the complexity of gene-environment-epigenetic interactions contributing to human health and disease. As epigenetic profile changes with age it is important to use age-matched cases and controls, disease discordant MZ twin pairs being ideal. Our epigenetic projects take advantage of the existing, well phenotyped and genotyped trait discordant and concordant MZ and DZ twin pairs from the Finnish Twin Cohort Study, led by Professor Jaakko Kaprio.