SUMMARY/ABSTRACT Title: Investigating and improving performance of polygenic scores for cardiometabolic traits in Samoan adults Project Period: 2024-09-01--2026-08-31 The clinical utility of polygenic scores (PGSs) in individuals of Pacific Islander ancestry is unknown due to a paucity of Pacific Islanders participating in studies of PGSs. Specifically, the applicability of published polygenic scores for cardiometabolic disease risk and related biomarkers to clinical practice has not yet been evaluated. This gap in knowledge may further exacerbate health disparities in this population due to this unknown transfer- ability of findings from majority populations to individuals of Pacific Island ancestry. Therefore, the primary focus of this supplement is to provide the first ever examination of existing and development of PGSs of cardiometa- bolic traits in Pacific Islanders. This will be achieved through two primary aims—first, assessing the portability of existing PGSs for cardiometabolic health traits in Samoans, and second, to measure change in prediction power, and thus clinical utility, of PGSs that have been augmented to include Samoan-specific variation. Understanding the transferability of existing PGSs may shift how PGSs are translated into clinical practice by elucidating how much trait variation is due to underlying genetic components of cardiometabolic traits that are shared across populations and how much is context dependent. Clinical use of existing PGSs for individuals with Polynesian ancestry has the potential to exacerbate the health disparities that these populations already face in cardiomet- abolic disease prevention and treatment. Thus, this project will improve genomics-related health equity by ex- amining the portability of PGSs for cardiometabolic traits in a population that is systematically underrepresented in research and that faces alarmingly high rates of cardiometabolic disease. This project will provide the first ever characterization of the portability of existing PGSs for Polynesian populations which will inform clinical interpre- tation of these PGSs among individuals with Polynesian ancestry.

NARRATIVE Title: Investigating and improving performance of polygenic scores for cardiometabolic traits in Samoan adults Project Period: 2024-09-01 – 2026-08-31 The clinical utility of polygenic scores (PGSs) in individuals of Pacific Islander ancestry is unknown due to a paucity of Pacific Islanders participating in studies of PGSs. Therefore, the primary focus of this supplement is to provide the first ever examination of existing and development of PGSs of cardiometabolic traits in Pacific Islanders. This project will provide the first ever characterization of the portability of existing PGSs for Polynesian populations which will inform clinical interpretation of these PGSs among individuals with Polynesian ancestry.