Developing an oligogenic risk score for Alzheimer’s disease (adORS)

Polygenic risk score (PRS) has become a popular approach for estimating an individual’s genetic risk for disease, recently including Alzheimer’s disease. However, its limitations reveal the need to improve genetic modeling of the disease, i.e. pinpointing relevant genetic drivers for score calculation and improving interpretability and clinical utility. We propose a novel genetic risk score for Alzheimer’s disease (adORS), which—compared to PRS—combines a smaller set of more informative risk variants using known biomarkers to better predict those with high or low risk of disease, as well as mild cognitive impairment (MCI) conversion to AD.