Advances in polygenic score methods and applications in psychiatric genetics

We propose a symposium WCPG 2023 to address recent methodological advances in polygenic scores (PGS) methods and their applications to study the etiology of psychiatric disorders. In recent years, PGS have emerged as a powerful tool for both quantifying genetic risk and deciphering the genetic architecture of psychiatric disorders. However, the predictive accuracy of PGS is limited by heritability, as it only accounts for the genetic contribution to risk. Moreover, their accuracy is significantly influenced by factors such as sample ascertainment, sample size, and individual genetic ancestry. These factors can lead to biased or mis-calibrated individual risk estimates and limit their suitability for clinical practice, highlighting the need for innovative approaches to address these limitations. This symposium focuses on recent developments in polygenic score methodology and applications in psychiatric genetics, combined with a discussion on their future. Our method-focused symposium will bring together distinguished experts Dr. Jian Zeng, Dr. Florian Privé, Dr. Clara Albiñana, Dr. Paul O'Reilly, Prof. Bjarni Vilhjalmsson, and Prof. Naomi Wray to share their knowledge and experience on the latest advancements, challenges, and future directions in the field of predictive genetics for psychiatric disorders. The session will be chaired by Bjarni Vilhjalmsson and Jian Zeng, and Naomi Wray will be a discussant. The proposed speaker order and titles are as follows. ``Recent and future updates to LDpred2 for polygenic scores and inference” - Florian Privé. Florian will discuss how Bayesian polygenic models can be used to both derive polygenic scores, as well as infer genetic architecture, and perform fine-mapping. ``Leveraging functional genomic annotations and genome coverage to improve polygenic prediction of complex traits within and between ancestries" - Jian Zeng. Jian will discuss how incorporating functional information can significantly improve prediction accuracies when considering millions of variants. ``Increasing polygenic prediction with an agnostic multi-PGS method that leverages hundreds of polygenic scores" - Clara Albiñana. Clara will discuss how leveraging GWAS from hundreds of correlated outcomes can significantly improve genomic prediction for psychiatric disorders. “Using polygenic scores to infer the genetic architecture in the tails of complex traits” - Paul O'Reilly. Paul will discuss how polygenic scores can be used to infer the relative abundance of polygenic and rare etiology in complex trait tails, where rare variants and disease are concentrated due to natural selection. Discussant Naomi Wray will discuss and highlight some issues raised in the presentations In conclusion, we believe that our proposed symposium will provide an engaging and comprehensive overview of the current state of technical developments in polygenic score methods and their applications in psychiatric disorders.