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.
