Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain
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 stigm...
Published in: | Frontiers in Pain Research |
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Online Access: | http://dx.doi.org/10.3389/fpain.2022.1021963 https://www.frontiersin.org/articles/10.3389/fpain.2022.1021963/full |
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crfrontiers:10.3389/fpain.2022.1021963 2024-04-21T08:01:02+00:00 Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain Aroke, Edwin N. Hobson, Joanna M. Ptacek, Travis Jackson, Pamela Goodin, Burel R. National Institutes of Health 2022 http://dx.doi.org/10.3389/fpain.2022.1021963 https://www.frontiersin.org/articles/10.3389/fpain.2022.1021963/full unknown Frontiers Media SA https://creativecommons.org/licenses/by/4.0/ Frontiers in Pain Research volume 3 ISSN 2673-561X journal-article 2022 crfrontiers https://doi.org/10.3389/fpain.2022.1021963 2024-03-26T08:33:25Z 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 ... Article in Journal/Newspaper DML Frontiers (Publisher) Frontiers in Pain Research 3 |
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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 ... |
author2 |
National Institutes of Health |
format |
Article in Journal/Newspaper |
author |
Aroke, Edwin N. Hobson, Joanna M. Ptacek, Travis Jackson, Pamela Goodin, Burel R. |
spellingShingle |
Aroke, Edwin N. Hobson, Joanna M. Ptacek, Travis Jackson, Pamela Goodin, Burel R. Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain |
author_facet |
Aroke, Edwin N. Hobson, Joanna M. Ptacek, Travis Jackson, Pamela Goodin, Burel R. |
author_sort |
Aroke, Edwin N. |
title |
Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain |
title_short |
Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain |
title_full |
Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain |
title_fullStr |
Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain |
title_full_unstemmed |
Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain |
title_sort |
genome-wide dna methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain |
publisher |
Frontiers Media SA |
publishDate |
2022 |
url |
http://dx.doi.org/10.3389/fpain.2022.1021963 https://www.frontiersin.org/articles/10.3389/fpain.2022.1021963/full |
genre |
DML |
genre_facet |
DML |
op_source |
Frontiers in Pain Research volume 3 ISSN 2673-561X |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3389/fpain.2022.1021963 |
container_title |
Frontiers in Pain Research |
container_volume |
3 |
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1796941395463766016 |