Epigenomic and Gene Expression Signatures of Racial Differences in Chronic Low Back Pain

项目总结/摘要 慢性腰痛（cLBP），持续超过12周，与高货币（高达2000亿美元）有关 每年在美国）和非货币的社会和个人成本，如生活质量下降，降低 自我价值、生产力下降、耻辱、抑郁和加速衰老。在美国的个人， 认同非裔美国人/黑人种族背景经历更频繁，更严重，更残疾 cLBP与其他种族群体相比，特别是高加索人/白人。这种差异强调了 黑人的cLBP负担显著更高，由于社会经济地位低而加剧， 耻辱和歧视。然而，在以下方面的知识存在差距：1）导致和 维持cLBP的种族差异，和2）这些因素对更差的cLBP结果的相对贡献， 黑人遗传和环境因素影响慢性疼痛。DNA甲基化（DNAm）是一种 环境因素改变哪些基因被打开或关闭的表观遗传机制， 改变DNA序列根据我们的初步数据和文献，我们建议前瞻性地 从正在进行的母研究（R 01 MD 010441）中采集血样，以阐明导致 并维持cLBP的种族差异。我们的中心假设是，黑人经历更多的负面影响， 环境暴露比白人在美国，这可能会导致DNA的变化，造成和维持 更严重和禁用cLBP黑人。我们的主要目标是发现新的表观遗传和基因 cLBP种族差异的基础表达机制。我们将使用尖端技术，减少 代表性亚硫酸氢盐测序（RRBS）和RNA测序（RNA-Seq），以确定DNAm和基因 表情变化。我们的具体目标是：1）确定DNA和基因的种族差异 在有和没有cLBP的情况下黑人和白人之间的表达，以及2）确定DNA m和基因 表达模式与应激性环境暴露以及cLBP的严重性相关。对我们 知识，没有研究检查心理，社会经济地位，表观基因组学和转录数据 在一个种族多样的cLBP成人样本中。结合来自家长研究的严格的社会心理数据， 从这项辅助研究中获得的分子信息，代表了种族差异研究的范式转变 在cLBP中。这个项目意义重大，因为它将增加我们对cLBP的了解，并可能为干预提供信息。 研究扭转推动cLBP结果的表观基因组变化，这将使所有人的生活质量更好 cLBP患者

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.