The PRIMED Consortium: Reducing disparities in polygenic risk assessment
Iftikhar J. Kullo, Matthew P. Conomos, Sarah C. Nelson, Sally N. Adebamowo, Ananyo Choudhury, David V. Conti, Stephanie M. Fullerton, Stephanie M. Gogarten, Ben Heavner, Whitney Hornsby, Eimear E. Kenny, Alyna Khan, Amit V. Khera, Yun Li, Iman K. Martin, Josep M. Mercader, Maggie C. Y. Ng, Laura M. Raffield, Alex P. Reiner, Robb Rowley, Daniel J. Schaid, Adrienne M. Stilp, Ken Wiley, Riley Wilson, John S. Witte, Pradeep Natarajan, Sally Adebamowo, Clement Adebamowo, Nicholette Allred, Paul Auer, Jennifer Below, Palwende Romuald Boua, Kristin Boulier, Michael Bowers, Joseph Breeyear, Nilanjan Chatterjee, Tinashe Chikowore, Jaewon Choi, Ananyo Choudhury, Matthew Conomos, David Conti, Nancy Cox, Sinead Cullina, Burcu Darst, Aaron Deutsch, Yi Ding, Todd Edwards, Eleazar Eskin, Segun Fatumo, Jose Florez, Nelson Freimer, Stephanie Fullerton, Tian Ge, Daniel Geschwind, Chris Gignoux, Stephanie Gogarten, Mark Goodarzi, Xiuqing Guo, Christopher Haiman, Neil Hanchard, Scott Hazelhurst, Ben Heavner, Susan Heckbert, Jibril Hirbo, Whitney Hornsby, Kangcheng Hou, Qinqin Huang, Alicia Huerta, Guoqian Jiang, Katherine Johnston, Linda Kachuri, Takashi Kadowaki, Abram Bunya Kamiza, Eimear Kenny, Sarah Kerns, Alyna Khan, Joohyun Kim, Iain Konigsberg, Charles Kooperberg, Matt Kosel, Peter Kraft, Iftikhar Kullo, Soo-Heon Kwak, Leslie Lange, Ethan Lange, Loic Le Marchand, Hyunsuk Lee, Aaron Leong, Yun Li, Meng Lin, Kirk Lohmueller, Ruth Loos, Kevin Lu, Ravi Mandia, Alisa Manning, Alicia Martin, Iman Martin, Hilary Martin, Rasika Mathias, James Meigs
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.