Comprehensive Biological Data in NCHAT BIO: Chronic Stress, Inflammation, and Epigenetic Aging - Health disparities are preventable and identifying their social determinants and underlying mechanisms is of high scientific priority. A 2020 National Academies of Sciences report articulated a clear national agenda to target health disparities among the sexual minority (SM) population, and there is a renewed focus on research to address disparities among racial and ethnic minority individuals. Critically, data on biological mechanisms linking stress and health in the SM population are limited. We will assess inflammation via serum interleukin(IL)-6 and C-reactive protein (CRP). Low-grade, chronic inflammation is implicated in age-associated frailty, morbidity, mortality, and accelerated epigenetic aging.36 Epigenetic age, is a highly novel and robust predictor of multiple diseases, longevity, and all-cause mortality. Examining epigenetic clocks through DNA methylation offers a cutting-edge approach allowing us to answer critical questions: Does SM stress accelerate aging? Can stigma and discrimination propel molecular aging and shorten health span (the length of time that a person is healthy—not just alive)? Capitalizing on a time-sensitive, unparalleled opportunity to add biological data collection to the National Couples’ Health and Time Study (NCHAT) to create additional data for the NCHAT Stress Biology Study (NCHAT-BIO), we aim to fill these empirical gaps. Funded by NIH, NCHAT is the only longitudinal, probability, population-representative study (N = 3,642, ages 22-67, 50% women) with representation of heterosexual (55%), sexual minority (45%), non-Hispanic white (62%), and racial and ethnic minority (38%) coupled adults with comprehensive psychosocial measurement. This project advances innovative health research by combining survey data on stressor exposures, psychological health, and health behaviors with biological data from an estimated 2000 of NCHAT’s respondents. Aim 1: Delineate differences in epigenetic aging and inflammation by sexual orientation and test interaction effects of sex and race/ethnicity. Aim 2: Determine effects of sexual minority stressors on epigenetic aging and inflammation. Aim 3: Identify modifiable factors linking sexual orientation and sexual minority stressors with epigenetic aging and inflammation. Sexual minorities face significantly greater risk for chronic health conditions than heterosexuals. The biological underpinnings of these group differences have been minimally studied representing an unacceptable gap in knowledge. This study offers the remarkable opportunity to examine epigenetic aging and inflammation in a large, US-representative sexual minority and heterosexual population, permitting crucial tests of mechanisms linking stress and health, and interaction effects of race/ethnicity and sex. This research promises to uncover modifiable treatment targets to address health disparities. The resultant assays will be publicly available to other researchers via ICPSR offering an unrivaled resource for future researchers. By leveraging NCHAT to create NCHAT-BIO, this is a singular and time urgent opportunity.