Calibrated rare variant genetic risk scores for complex disease prediction using large exome sequence repositories

ABSTRACT Rare variants are collectively numerous and may underlie a considerable proportion of complex disease risk. However, identifying genuine rare variant associations is challenging due to small effect sizes, presence of technical artefacts, and heterogeneity in population structure. We hypothesized that rare variant burden over a large number of genes can be combined into predictive rare variant genetic risk score (RVGRS). We propose a …