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

项目摘要/摘要 持续超过12周的慢性下腰痛(CLBP)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、工作效率下降、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、更致残 CLBP与其他种族群体，特别是高加索人/白人相比。这种差异突显了 黑人的cLBP负担要高得多，这一点因社会经济地位低而加剧， 耻辱和歧视。然而，在与1)引起和发展的机制有关的知识上存在差距 维持cLBP的种族差异，以及2)这些因素对cLBP结果较差的相对贡献 黑人。遗传和环境因素会影响慢性疼痛。DNA甲基化(DNaM)是一种 一种表观遗传机制，通过这种机制，环境因素改变了哪些基因被开启或关闭而没有 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 从正在进行的父母研究(R01MD010441)中采集血液样本，以阐明导致 并维持着cLBP的种族差异。我们的中心假设是黑人经历了更多的不利因素 美国白人的环境暴露，这可能会导致并持续引起dNaM变化 更严重，使黑人无法使用cLBP。我们的主要目标是发现新的表观遗传学和基因 CLBP中种族差异的表达机制。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 表情发生了变化。我们的具体目标是1)确定种族群体在dNaM和基因上的差异 有无cLBP的黑人和白人之间的表达；2)确定dNaM和基因 表达模式与应激性环境暴露以及cLBP的严重程度有关。致我们的 知识，没有研究检查心理、社会经济地位、表观基因组和转录组数据 在不同种族的慢性下腰痛成人样本中。结合来自父母研究的严格的心理社会数据， 利用这项辅助研究的分子信息，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 逆转推动cLBP结果的表观基因组变化的研究，这将使所有人的生活质量更好 慢性下腰痛患者。

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.