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

Aroke, Edwin N.; Jackson, Pamela Braboy; Meng, Lingsong; Huo, Zhiguang; Overstreet, Demario S; Penn, Terence; Quinn, Tammie; Cruz-Almeida, Yenisel; Goodin, Burel R.

doi:10.1016/j.ynpai.2022.100086

Cited by 8 publications

(4 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The q -values are the equivalence of false discovery rate (FDR) in methylKit . Consistent with prior work, we defined differentially methylated loci (DML) as DMCs with q < 0.01 and at least 10% methylation difference between groups ( 23 , 24 , 38 ).…”

Section: Discussionmentioning

confidence: 81%

“…These heritable processes are tissue specific and play an essential role in physiological and pathophysiological processes (22). Growing evidence correlate differential DNAm of genes involved in stress regulation and neuro-inflammatory processes with non-specific cLBP (23)(24)(25). However, evidence of the relationship between internalized stigma and DNAm changes in individuals with non-specific cLBP is lacking so far.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain

et al. 2022

Self Cite

View full text Add to dashboard Cite

Non-specific chronic low back pain (cLBP) represents a common musculoskeletal condition with no identifiable cause. It cannot be diagnosed with conventional neuroimaging techniques such as computerized tomography (CT). The diagnostic uncertainty that characterizes non-specific cLBP can lead to stigmatizing responses from others that can become internalized Among individuals with non-specific cLBP, internalized stigma is associated with greater pain intensity and disability. Yet, no study has examined the biological mechanism linking high internalized stigma to worse outcomes in individuals with non-specific cLBP. We aimed to identify differentially methylated loci (DML), enrichment pathways, and associated network interactions among individuals with non-specific cLBP experiencing low vs. high internalized stigma. We examined DNA methylation in whole blood samples from 48 adults, ages 19–85, using reduced representation bisulfite sequencing (RRBS). After controlling for age, sex, race, and multiple testing, differentially methylated loci (DML) differed in adults with low vs. high internalized stigma by at least 10% and q < 0.01 in 3,665 CpG sites: 2,280 hypomethylated and 1,385 hypermethylated. Gene ontology (GO) analyses of the annotated genes from these sites revealed significant enrichment of 274 biological processes, 29 cellular components, and 24 molecular functions (adjusted p < 0.05). The top enriched molecular functions regulate protein binding and DNA binding of transcription factor activity. Pathway analyses indicated that many functional genomic pathways, including Hippo Signaling, Melanogenesis, and Pathways in Cancer, were enriched with differentially methylated genes. Also, there was a significant interaction between relevance pathways such as P53, mTOR, PI3K-Akt, and Wnt signaling pathways. These pathways have previously been associated with neuroinflammation, neurodegeneration, and stress-related conditions. Thus, findings point to possible stress-induced DNAm changes as the link between high levels of internalized stigma and worse outcomes in adults with non-specific cLBP.

show abstract

Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…41 Other investigators have linked epigenetic age acceleration with chronic musculoskeletal pain such as knee osteoarthritis. [42][43][44] Given that DNA methylation alterations of stress-related inflammatory process correlate with cLBP 5,45,46 and insomnia, 47 it is possible that insufficient sleep quality that characterizes insomnia epigenetically induces inflammatory processes that accelerate aging, sustaining worse cLBP.…”

Section: Discussionmentioning

confidence: 99%

The pace of biological aging helps explain the association between insomnia and chronic low back pain

Aroke,

Wiggins,

Hobson

et al. 2023

Mol Pain

Self Cite

View full text Add to dashboard Cite

Chronic low back pain (cLBP) is associated with insomnia and advanced age. Emerging evidence suggests that the severity of both sleep disorders (like insomnia) and chronic pain are associated with a faster pace of biological aging. We aimed to determine whether the pace of biological age mediates the relationship between insomnia and the impact of cLBP in a sample of community-dwelling adults ages 19 to 85 years. Participants (49 with no pain, 32 with low-impact pain, and 37 with high-impact pain) completed sociodemographic, pain, insomnia, and short physical performance battery assessments. We calculated the pace of biological aging using DunedinPACE from blood leukocyte DNA. On average, individuals with high-impact cLBP had significantly faster biological aging than those with low-impact and no chronic pain (p < 0.001). Bivariate associations of DunedinPACE scores with insomnia severity and functional performance were significant at p < 0.01 (rs = 0.324 and -0.502, respectively). After adjusting for race and sex, the association of insomnia severity and the impact of cLBP was partially mediated by the pace of biological aging (β = 0.070, p < 0.001). Also, the association of insomnia severity with functional performance was partially mediated by the pace of biological aging (β = -0.105, p < 0.001). Thus, insomnia remains strongly predictive of cLBP outcomes, and the pace of biological aging helps explain this association. Future prospective studies with repeated assessments are needed to uncover the directionality of these complex relationships and ultimately develop interventions to manage cLBP.

show abstract

“…67 Aroke et al compared DNA methylation of 50 cLBP patients and 50 healthy individuals and found that most differentially methylated genes were located in CpG islands and promoter regions for genes involved in immune signaling, endochondral ossification, G-protein coupled transmissions, pain processing, and neuronal differentiation. 68,69 Methylation of genes related to neuronal differentiation, growth, and plasticity may also be involved in impaired conditional pain modulation in cLBP patients. 70 Studies from 2021 suggest a role of lymphocytes in cLBP.…”

Section: Pain Medicinementioning

confidence: 99%

Protocol for Biospecimen Collection and Analysis Within the BACPAC Research Program

et al. 2022

View full text Add to dashboard Cite

The Biospecimen Collection and Processing Working Group of the NIH HEAL Initiative BACPAC Research Program was charged with identifying molecular biomarkers of interest to chronic low back pain (cLBP). Having identified biomarkers of interest, the Working Group worked with the New York University Grossman School of Medicine, Center for Biospecimen Research and Development—funded by the Early Phase Pain Investigation Clinical Network Data Coordinating Center—to harmonize consortium-wide and site-specific efforts for biospecimen collection and analysis. Biospecimen collected are saliva, blood (whole, plasma, serum), urine, stool, and spine tissue (paraspinal muscle, ligamentum flavum, vertebral bone, facet cartilage, disc endplate, annulus fibrosus, or nucleus pulposus). The omics data acquisition and analyses derived from the biospecimen include genomics and epigenetics from DNA, proteomics from protein, transcriptomics from RNA, and microbiomics from 16S rRNA. These analyses contribute to the overarching goal of BACPAC to phenotype cLBP and will guide future efforts for precision medicine treatment.

show abstract

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

Cited by 8 publications

References 78 publications

Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain

Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain

The pace of biological aging helps explain the association between insomnia and chronic low back pain

Protocol for Biospecimen Collection and Analysis Within the BACPAC Research Program

Contact Info

Product

Resources

About