PROJECT SUMMARY The purpose of this administrative supplement proposal is to expand the studies in our parent project R03DE033541-01, Leveraging All of Us data to unravel the interconnectedness between dental and systemic disease. In the parent project, we are conducting a large-scale study leveraging and integrating high-quality clinical (dental and medical), genomic, and demographic data available from >250,000 participants in the All of Us Research Program (AoU) to identify host factors most likely contributing to a combined phenotype of dental + systemic disease. For this administrative supplement, we propose to expand the above studies to include AoU participant survey data and employ an intersectional approach incorporating analyses of lifestyle, health care access and utilization, and other social determinants of health (SDOH), in order to identify the SDOH domains most likely to intersect with the dental and systemic conditions being assessed on the parent project, with a focus on women’s health. Several lines of evidence have shown that SDOH are linked to differences in prevalence of oral and systemic disease and reduced opportunities for health and health-related quality of life, particularly in women. However, there is a lack of studies integrating individual biological (e.g., genomic, sex at birth), and nonbiological (e.g. SDOH) aspects thereby precluding our ability to understand the full spectrum of the common causes and pathways of dental/systemic disease and their interactions as contributors to differential disease predisposition or manifestation. Here, we will test the hypothesis that non-biological SDOH factors may intersect with biological sex to influence disease predisposition and/or clinical manifestation. We will integrate SDOH data available for the AoU participants that are being used in our parent project to the clinical and genomic data obtained and apply a multidimensional analysis framework to explore the intersectional effects of biological and non-biological (SDOH) factors and contributing to a combined phenotype of dental + systemic disease in males and females. This study represents a major advance in the field by creating a roadmap for integrating clinical, genomic, demographic and survey data from a large and diverse population in the AoU program to develop a more comprehensive picture of the factors contributing to oral and systemic health/disease relationships between the sexes. This proposal addresses the Trans-NIH Strategic Plan for Women’s Health Research goal #1 Advancing rigorous research, and the NIDCR’s Strategic Priorities #1 Integrate Oral and General Health, and #2 Precision Dental Medicine.