PROJECT SUMMARY / ABSTRACT Chronic low back pain (cLBP), lasting more than 12 weeks, is associated with high monetary (up to $200 billion annually in the USA) and non-monetary societal and personal costs such as decreased quality of life, lowered self-worth, reduced productivity, stigma, depression, and accelerated aging. Individuals in the USA who identify with an African American/Black racial background experience more frequent, severe, and disabling cLBP compared to other racial groups, particularly Caucasians/Whites. This difference underscores the substantially higher burden of cLBP among Blacks, which are exacerbated by low socioeconomic status, stigma, and discrimination. However, there is a gap in knowledge relating to 1) the mechanisms that cause and sustain racial differences in cLBP, and 2) the relative contributions of these factors for worse cLBP outcomes in Blacks. Genetic and environmental factors influence chronic pain. DNA methylation (DNAm) is a type of epigenetic mechanism by which environmental factors alter which genes are turned-on or turned-off without changing the DNA sequence. Informed by our preliminary data and literature, we propose to prospectively collect blood samples from an ongoing parent study (R01MD010441) to elucidate the mechanism that causes and sustains racial differences in cLBP. Our central hypothesis is that Blacks experience more adverse environmental exposures than Whites in the USA, which may induce DNAm changes that cause and sustain more severe and disabling cLBP for Blacks. Our primary objective is to uncover novel epigenetic and gene expression mechanisms that underlie racial differences in cLBP. We will use cutting edge technology, reduced representation bisulfite sequencing (RRBS) and RNA-sequencing (RNA-Seq), to determine DNAm and gene expression changes. Our specific aims are 1) to determine racial group differences in DNAm and gene expression between Blacks and Whites with and without cLBP, and 2) to determine if DNAm and gene expression patterns are associated with stressful environmental exposures as well as severity of cLBP. To our knowledge, no study has examined psychological, socioeconomic status, epigenomic, and transcriptomic data in a racially diverse sample of adults with cLBP. Combining rigorous psychosocial data from the parent study, with molecular information from this ancillary study, represents a paradigm shift in studies of racial differences in cLBP. This project is significant, as it will increase our understanding of cLBP and may inform intervention studies to reverse epigenomic changes that drive cLBP outcomes, which will allow a better quality of life for all patients with cLBP.