PQG Seminar

Rare variants significantly impact complex diseases. This presentation will first introduce SAIGE-GENE and SAIGE-GENE+, methodologies extending SAIGE to gene/region-based rare variant tests. These methods efficiently utilize mixed effects models to adjust for sample relatedness and saddlepoint approximations to account for case-control imbalance. SAIGE-GENE+ additionally incorporates functional annotations and collapsing of ultra-rare variants that can help to improve type I error control and power. In the second part of the talk, I will introduce our recent work to estimate effect sizes of rare variants. The method, RareEffect, uses an empirical Bayesian approach that estimates gene/region-level heritability and then an effect size of each variant. We also show the effect sizes obtained from our model can be leveraged to improve the performance of polygenic scores.