The PRIMED Consortium: Reducing disparities in polygenic risk assessment. Am J Hum Genet 2024 Dec 05;111(12):2594-2606
Date
11/20/2024Pubmed ID
39561770Pubmed Central ID
PMC11639095DOI
10.1016/j.ajhg.2024.10.010Scopus ID
2-s2.0-85210411516 (requires institutional sign-in at Scopus site)Abstract
By improving disease risk prediction, polygenic risk scores (PRSs) could have a significant impact on health promotion and disease prevention. Due to the historical oversampling of populations with European ancestry for genome-wide association studies, PRSs perform less well in other, understudied populations, leading to concerns that clinical use in their current forms could widen health care disparities. The PRIMED Consortium was established to develop methods to improve the performance of PRSs in global populations and individuals of diverse genetic ancestry. To this end, PRIMED is aggregating and harmonizing multiple phenotype and genotype datasets on AnVIL, an interoperable secure cloud-based platform, to perform individual- and summary-level analyses using population and statistical genetics approaches. Study sites, the coordinating center, and representatives from the NIH work alongside other NHGRI and global consortia to achieve these goals. PRIMED is also evaluating ethical and social implications of PRS implementation and investigating the joint modeling of social determinants of health and PRS in computing disease risk. The phenotypes of interest are primarily cardiometabolic diseases and cancer, the leading causes of death and disability worldwide. Early deliverables of the consortium include methods for data sharing on AnVIL, development of a common data model to harmonize phenotype and genotype data from cohort studies as well as electronic health records, adaptation of recent guidelines for population descriptors to global cohorts, and sharing of PRS methods/tools. As a multisite collaboration, PRIMED aims to foster equity in the development and use of polygenic risk assessment.
Author List
Kullo IJ, Conomos MP, Nelson SC, Adebamowo SN, Choudhury A, Conti D, Fullerton SM, Gogarten SM, Heavner B, Hornsby WE, Kenny EE, Khan A, Khera AV, Li Y, Martin I, Mercader JM, Ng M, Raffield LM, Reiner A, Rowley R, Schaid D, Stilp A, Wiley K, Wilson R, Witte JS, Natarajan P, Polygenic Risk Methods in Diverse Populations (PRIMED) ConsortiumAuthor
Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Genetic Predisposition to DiseaseGenome-Wide Association Study
Genotype
Humans
Multifactorial Inheritance
Neoplasms
Phenotype
Risk Assessment
Risk Factors