Project Summary The Multiethnic Observational Study in American Asian and Pacific Islander Communities (MOSAAIC) is a pioneering initiative proposed to address significant gaps in health research for Asian American, Native Hawaiian, and Pacific Islander populations. Historically underrepresented in biomedical research, these groups face unique health challenges and disparities that require targeted investigation. The National Heart, Lung, and Blood Institute (NHLBI) has initiated this comprehensive longitudinal cohort study, involving 10,000 participants, to transform our understanding of cardiometabolic and mental health disparities within these populations. We propose to collect and analyze PAXgene RNA and Peripheral Blood Mononuclear Cells (PBMCs) from 10,000 participants to advance our understanding of cardiometabolic and mental health disparities in Asian American, Native Hawaiian, and Pacific Islander populations. PAXgene Collection and Analysis (Aim 1): We will collect PAXgene RNA tubes from participants during both the UG and UH phases. The central lab service will supply the tubes to the Clinical or Community Field Studies (CCFCs). Tubes will be stored following the standard protocol to ensure sample integrity and then shipped to the central lab for RNA extraction. This high-quality RNA will be used for whole-blood transcriptomics to identify gene expression patterns and provide insights into health disparities. Advanced bioinformatics tools will integrate these data with other genomic and clinical data to uncover biomarkers and therapeutic targets. PBMC Collection and Analysis (Aim 2): We will collect PBMCs from 9,500 participants during the UH phases. The central lab will provide the necessary materials, and the CCFCs will process whole blood samples to isolate PBMCs. We will then isolate specific cell subsets for transcriptomics analysis, measure immune cell distributions using multiparameter flow cytometry, and assess immune function by exposing PBMCs to specific stimuli. Additionally, we will explore transforming PBMCs into induced pluripotent stem cells (iPSCs) for organ- specific research, enabling detailed investigations into the unique biological characteristics of these populations and informing targeted interventions.