Polygenic risk score (PRS) have the potential to stratify individuals at high risk of disease. Using a PRS in conjunctioon with traditional risk factors has been shown to enhance the risk prediction of disease outcomes in multiple studies. Exploiting genetic variants associated with disease risk from multiple genome-wide association studies for different risk factors and disease have been reported to outperform single-disease PRS. We hypothesis that with the inclusion of genetic variants associated with modifiable risk factors and biomarkers for disease onset and progression, PRS may provide enhanced risk stratification before the presence of risk factors and enable disease prevention in early life.

In this study, we will develop both single and multi-trait PRS models for complex traits in the UK Biobank and validate their performance in terms of prediction and stratification over the life course using data from participants in the ALSPAC cohort study.