Dr. Gunn will discuss findings from a study leveraging data from Million Veterans Program and All of Us Research Program to compare methods for building polygenic scores (PGS) for multi-ancestry populations across multiple traits.

Co-first authors Drs. Kullo and Nelson will present an introduction and overview of the NIH-funded PRIMED Consortium, which is working to improve polygenic risk prediction of a range of health outcomes across diverse, global populations. The presentation will cover design and rationale, organization and progress of Consortium activities, methodological innovations, and initial Consortium findings and products.

Dr. Costain will discuss findings from systematically assessing rare canonical splice site variants in blood expressed genes in a cohort of individuals who underwent genome sequencing and RNA-seq. The team found that up to 1 in 4 variants may not cause loss-of-function, and that in silico predictions using established tools and published guidelines were often discordant with RNA-seq data.

Erin Thorpe Venti will present findings from an observational, retrospective analysis of 1,004 underserved individuals from 8 countries with suspected rare genetic disease who received clinical genome sequencing (cGS) through the iHope program, a philanthropic testing access program.

Dr. Gabrielle Lemire will discuss exome copy number variant (CNV) detection, analysis and classification on a cohort of 6,633 families with undiagnosed rare genetic disorders. With the resolution provided by exome sequencing, they identified a causative CNV in 2.6% of families and assessed CNV pathogenicity by applying an advanced classification approach.