Harnessing DNA methylation variation between populations to understand disease discordance across ancestries.

DNA methylation (DNAm) plays a central role in gene regulation. It helps to define how cells respond to genetic and environmental signals and, ultimately, contributes to the whole system’s health and disease status. Levels of DNAm differ from one person to another. Some of these variation in DNAm levels is caused by genetic or environmental factors. Understanding the variation in DNAm levels will helps us to understand that why the disease risk and response to treatment is different for different population. Evaluating DNAm variation in diverse population groups allows comparison across varying genetic and environmental exposure profiles.

This will allow the identification of molecular mechanisms that underpin difference in disease prevalence across the global population. Aim is to map genetic and environmental determinants of human DNAm variation to understand mechanisms of DNAm variability. We will generate a catalogue of genetic associations with DNAm across populations worldwide.  This will help us to understand functional role of genetic variability in descending disease risk.

The second aim of the project is to understand mechanisms of disease and differences in disease and risk in different population. This research builds a global partnership of teams to bring together genetic and epigenetic data collected from individuals worldwide. A key aspect of this proposal is building equitable partnerships between these teams. This is essential in order to build capacity for research in genetically diverse datasets.

Identification of common and context-specific mechanisms of health and disease mediated by DNAm is of high health impact because it will enable actions to reduce global health disparity and inequity via targeted interventions or treatments.