SUMMARY/ABSTRACT Title: Lipidomics and structural genomics of cardiometabolic health in Samoan adults Project Period: 09/01/2023–08/31/2027 Pacific Islanders, such as Samoans, are disproportionally burdened by cardiometabolic disease yet are un- derrepresented as participants in health research generally, and in genomics research specifically. In this project we will expand the knowledge of lipidomic and genetic structural variation present in Samoans to understand the relationships between the lipidome, simple nucleotide variation, structural genetic, modifiable risk factors, and cardiometabolic health. In our first aim, we will determine associations between comprehensive serum lipid pro- files and both simple nucleotide variation and cardiometabolic traits in 4,300 Samoan adults from Samoa and American Samoa. To achieve this, we will first generate comprehensive lipidomic data, then characterize asso- ciations between the lipidome, modifiable risk factors, and cardiometabolic phenotypes, conduct lipidome-wide association studies of known genetic determinants of lipid variation, and perform genome-wide association stud- ies of the lipidome. In our second aim, we will evaluate associations between structural genetic variation and both comprehensive lipid profiles and cardiometabolic phenotypes by calling structural variation in 1,285 se- quenced Samoan adults, imputing that variation into the larger set of the aforementioned 4,300 Samoan adults, examining associations between structural variation near known genetic determinants of lipidome and cardi- ometabolic variation, and examining associations between genome-wide structural variation and the lipidome and cardiometabolic phenotypes. In our third aim, we will conduct exploratory integrative analyses to identify systems-level patterns among the layers of information available and gathered in the first two aims. Finally, in our fourth aim, we will propose and lead collaborative investigations of our findings with collaborators among the TOPMed Program. our active participation with the Program will enlarge the range of multi-ancestry analyses possible among the participating studies and broaden the impact of this work beyond Samoa. Our discoveries will improve our understanding of the basic biology of lipids and downstream cardiometabolic health outcomes, as well as identify potential targets for interventions to improve cardiometabolic health.

NARRATIVE Title: Lipidomics and structural genomics of cardiometabolic health in Samoan adults Project Period: 04/01/2023–03/31/2027 This project will explore the relationships between lipids, genes, environment, heart health, and obesity-related traits among Samoans, a Pacific Islander population with high rates of diseases like type 2 diabetes and heart disease. This study will focus on the lipidome, made up of biologically simpler lipid species than conventional cholesterol measurements, and on structural changes in the genome, which are expected to have larger effects than simpler genetic variants. Our discoveries will improve our understanding of the basic biology of lipids and how they affect heart health and obesity-related traits. We will also identify potential targets for interventions to improve health overall.