Background
Every cell in the body contains the same DNA, yet can develop and function in highly specialised ways. A pivotal way of enabling this is through epigenetic modification, such as DNA methylation, which help mark active and inactive regions of the genome with cell type and developmental specificity. These marks can change with age, environment and health, and act as a biological record of how our bodies respond to both genetic and lifestyle factors. Increasingly, scientists recognise that epigenetic variation can modify disease expression or be indicators of differential disease response. This may explain, in part, why people with the same genetic condition or risk factor often have different symptoms or outcomes.
Novelty & Importance
This project focuses on disorders caused by changes in genes that control chromatin structure, the molecular machinery that organises DNA and regulates access to genes. These proteins do not direct alter DNA methylation, but respond to its signals and can indirectly lead to altered methylation states. These chromatin-regulator disorders often cause intellectual disability and other health problems, but the reasons for their variability remain unclear. By studying how normal variation in epigenetic patterns affects health, we can better understand why some individuals develop more severe symptoms or additional conditions such as diabetes or psychiatric illness. The research takes a new approach: it begins with large population datasets to discover how genetic and epigenetic variation at chromatin-regulator genes influences molecular signs of ageing and disease risk. The same analyses are then applied to patient data to see whether these epigenetic features can predict disease progression or comorbidity.
Aims and Objectives:
– Identify how genetic and epigenetic variation at chromatin-regulator genes affects biological ageing and health-related traits.
– Develop methylation-based measures that summarise risk for common comorbidities.
– Build predictive, data-driven tools to help anticipate health outcomes and guide personalised care.