Approved Research

Evidence for Polygenic Background Selection and Epistasis in Human Complex Traits

Lay summary

While some human diseases can be caused by one mutation in a single gene, increased risk for other diseases may require multiple genetic variants throughout someone's genome. By adding up the risk-associated variants in an individual's genome, we can get a 'polygenic risk score' (PRS) that helps describe how likely someone is to develop genetic disease based on their unique combination of genes. However, different genetic variants across the genome can interact to disproportionately affect disease risk, which is not currently accounted for in PRS calculation.

This research project will use data in the UK Biobank to stratify individuals into groups with high or low disease risk according to our genetic models, and then the actual clinical outcomes of the individuals will be inspected to see if the high-risk individuals are indeed at an unexpectedly high risk. This research will provide new insights into how to interpret genetic data in more clinically impactful ways.