The Pacific Ocean Native Observational (PONO) Health Legacy Study - PROJECT SUMMARY Hawai‘i is the most ethnically diverse state in the US. Native Hawaiians (NH), Pacific Islanders (PI) and Asian Americans (AsA) account for nearly 70% of the state’s population & it is home to >50% of all NHPI in the US. This UG3/UH3 proposal will establish a new prospective, multi-generational cohort to investigate cardiopulmonary & metabolic (CPM) health among NH & Micronesian PI in Hawai‘i. These 2 distinct, yet understudied, sub-populations have an excess burden of CPM disease outcomes. Diabetes mellitus (DM) occurs in 28% and preDM in 37% of NHPI (>20y.o.), suggesting >50% of NHPI have or are at-risk for DM. CVD mortality is 4-fold higher in NHPI with DM compared with nonDM. CVD mortality is the leading cause of death among NHPI. Despite decades of clinical & intervention studies among NHPI, CPM health inequities remain largely unchanged & is increasing among younger NH and PI people. Our proposal, the Pacific Ocean Native Observational (PONO) Health Legacy Study, will directly confront methodological challenges (i.e. racial aggregation, small sample size, etc.) of prior NHPI studies & will conduct innovative, technology-driven “populomics” approaches to change the course of CPM health disparities among NH & PI. Our approach builds on a strong interdisciplinary team of scientific & community-based leaders who bring decades of community, clinical, epidemiological & epigenomic expertise. We will work closely with the Coordinating Center to maximize the overall AsA-NHPI cohort’s ability to conduct studies of multiple hypotheses testing. Our specific aims (S.A.) are as follows: S.A.#1 (UG3): Establish a prospective, community-engaged, multi-generational population-based cohort study of 2,500 Native Hawaiians and Pacific Islanders in Hawai‘i. Our longstanding partnerships with clinical & community-based groups are primed & enthusiastic to recruit, retain & conduct standardized data & biological specimen collection that will invest in the health of future generations. S.A. #2 (UH3): Characterize the relationship of risk and resilience factors with clinical blood-based biomarkers of metabolic and immunologic function relevant to CPM conditions. Determine prevalence of CPM subclinical disease & conduct association studies of multi-level risk & resilience factors by CPM conditions. S.A. #3 (UH3): Assess the impact of CPM-associated risk and resilience factors on incident CPM- outcomes measured over time between Hawai‘i and continental populations of NH and PI in the AsA- NHPI cohort study. Determine incidence of CPM outcomes associated with multi-level risk/resilience factors & to compare data with relevant subpopulations in the overall AsANHPI cohort. The overall impact of the PONO study is its potential to transform health disparity research through novel “populomics” approaches in a representative population of AsANHPI in the US.