Differential DNA methylation in Black and White individuals with chronic low back pain enrich different genomic pathways

Abstract

Compared to Non-Hispanic Whites (NHWs), individuals who self-identify as Non-Hispanic Blacks (NHBs) in the United States experience more severe and disabling chronic low back pain (cLBP). We hypothesized that differences in DNA methylation (DNAm) play a role in racial disparities in cLBP. PurposeTo determine the relationship between DNAm levels and racial group differences in adults with cLBP. Our study’s secondary purpose was to perform a race-stratified comparison of adults with cLBP and pain-free controls and identify functional genomic pathways enriched by annotated differentially methylated genes. Patients and MethodsWe recruited 49 NHBs and 49 NHWs (49 cLBP and 49 pain-free controls, PFCs), analyzed DNAm from whole blood using reduced representation bisulfite sequencing, and identified enriched genomic pathways. ResultsAmong participants with cLBP, we identified 2873 differentially methylated loci (DML; methylation differences of at least 10% and p < 0.0001), many of which were annotated to genes of importance to pain pathology. These DMLs significantly enriched pathways to involved in nociception/pain processing (Dopamine-DARPP32 Feedback in cAMP signaling, GABA Receptor Signaling, Opioid Signaling) and neuronal differentiation (e.g., Calcium Signaling, Axon Guidance Signaling, and Endocannabinoid Neuronal Synapse). Our race stratified analyses of individuals with cLBP versus PFCs revealed 2356 DMLs in NHBs and 772 DMLs in NHWs with p < 0.0001 and > 10% methylation difference. Ingenuity Pathway Analysis revealed that many pathways of significance to pain such as Corticotropin Releasing Hormone Signaling, White Adipose Tissue Browning, and GABA Receptor Signaling pathways, were more significant in NHBs than NHWs. ConclusionEven though an individual’s self-identified race is a social construct, not a biological variable, racism associated with that classification affects virtually every aspect of life, including disease risk. DNAm induced alterations in stress signaling pathways may explain worse pain outcomes in NHBs.