Using DNA methylation and genetic variation to investigate genetic burden

Many genetic diseases are not caused by a single mutation, but by the combined effects of multiple changes in the genome. Traditional methods for studying these diseases often focus only on DNA sequence variations, overlooking other important biological factors. One such factor is DNA methylation—a chemical modification that helps control when and how genes are turned on or off. My thesis research establishes a new approach that combines genetic variation with DNA methylation to better understand disease risk and causes of disease. We developed two scoring systems that capture these different types of biological information (BeWISE and BeMAGIC) and integrate them into a single measure called the MagicWise Index. This index helps identify genes that are more likely to play a role in disease. Using this method across several datasets, we were able to detect known disease-related genes and uncover potential new ones. By considering both genetic and epigenetic information, this approach provides a more complete picture of how diseases develop. The MagicWise Index offers a powerful new tool for researchers studying complex genetic diseases. Ultimately, this work may help improve disease diagnosis, guide future research, and support the development of more targeted treatments.