Genome-wide methylation analysis of a large population sample shows neurological pathways involvement in chronic widespread musculoskeletal pain

Livshits, Gregory; Malkin, Ida; Freidin, Maxim B.; Xia, Yudong; Gao, Fei; Wang, Jun; Spector, Timothy D.; Macgregor, Alexander; Bell, Jordana T.; Williams, Frances

doi:10.1097/j.pain.0000000000000880

Cited by 32 publications

(18 citation statements)

References 56 publications

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“…Using a sample of 1,708 MZ and DZ Caucasian adult twins (CWP prevalence of 19.9%), Livshits et al established longitudinally stable methylation bins (lsBINs) by repeated measurements taken ≥3 years apart. 55 In this largest EWAS on CWP conducted so far, the authors found the most significant lsBINs associated with CWP to be located within or around highly plausible candidates that have been previously suggested to be involved in the pathogenesis of CWP such as IL17A gene, the ADIPOR2 gene, and the TNFRSF13B gene. Being the first of their kind, preliminary results from these two methylation studies serve as a starting point to encourage further replication in large and independent population-based cohorts and subsequent biological investigation of the top findings to elucidate possible disease mechanisms.…”

Section: Resultsmentioning

confidence: 95%

Genetic and epigenetic epidemiology of chronic widespread pain

Kerr¹,

Burri²

2017

JPR

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The etiology underlying chronic widespread pain (CWP) remains largely unknown. An integrative biopsychosocial model seems to yield the most promising explanations for the pathogenesis of the condition, with genetic factors also contributing to disease development and maintenance. Here, we conducted a search of studies investigating the genetic and epigenetic epidemiology of CWP through electronic databases including Web of Science, Medline, PubMed, EMBASE, and Google Scholar. Combinations of keywords including CWP, chronic pain, musculoskeletal pain, genetics, epigenetics, gene, twins, single-nucleotide polymorphism, genotype, and alleles were used. In the end, a total of 15 publications were considered relevant to be included in this review: eight were twin studies on CWP, six were molecular genetic studies on CWP, and one was an epigenetic study on CWP. The findings suggest genetic and unique environmental factors to contribute to CWP. Various candidates such as serotonin-related pathway genes were found to be associated with CWP and somatoform symptoms. However, studies show some limitations and need replication. The presented results for CWP could serve as a template for genetic studies on other chronic pain conditions. Ultimately, a more in-depth understanding of disease mechanisms will help with the development of more effective treatment, inform nosology, and reduce the stigma still lingering on this diagnosis.

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Section: Resultsmentioning

confidence: 95%

Genetic and epigenetic epidemiology of chronic widespread pain

Kerr¹,

Burri²

2017

JPR

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“… 12 Epigenome-wide association study (EWAS) of this sample provided evidence of neurological pathway involvement in CWP. 14 Thus, the main aim of this study was 2-fold. First, implementing complex genomic, epigenomic, and metabolomic data analysis, we attempted to identify major molecular pathways affecting FI score variation.…”

Section: Introductionmentioning

confidence: 99%

Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways

Livshits

Malkin

Bowyer

et al. 2018

Pain

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“…fibromyalgia [16], and chronic widespread musculoskeletal pain [17]. Associations between neuropathic pain and DNA methylation, however, have not been well evaluated.…”

Section: Discussionmentioning

confidence: 99%

Association between Neuropathic Pain Characteristics and DNA Methylation of <em>TRPA1</em> in Human Peripheral Blood

Takenaka¹,

Sukenaga²,

Imasaka³

et al. 2019

Preprint

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Background: Elucidation of epigenetic mechanisms correlating with neuropathic pain in humans is crucial for the prevention and treatment of this treatment-resistant pain state. In the present study, associations between neuropathic pain characteristics and DNA methylation of the transient receptor potential ankyrin 1(TRPA1) gene were evaluated in chronic pain patients and preoperative patients. Methods: Pain and psychological states were prospectively assessed in patients who suffered chronic pain or were scheduled for thoracic surgery. Neuropathic characteristics were assessed using the Douleur Neuropathique 4 (DN4) questionnaire. DNA methylation levels of the CpG island in the TRPA1 gene were examined using whole blood. Results: Forty-eight adult patients were enrolled in this study. Increases in DNA methylation rates at CpG -51 showed positive correlations with increases in the DN4 score both in preoperative and chronic pain patients. Combined methylation rates at CpG -51 also significantly increased together with increase in DN4 scores. Conclusions: Neuropathic pain characteristics are likely associated with methylation rates at the promoter region of the TRPA1 gene in human peripheral blood.

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Genome-wide methylation analysis of a large population sample shows neurological pathways involvement in chronic widespread musculoskeletal pain

Abstract: Supplemental Digital Content is Available in the Text.We analysed epigenome-wide methylation in blood DNA in Caucasian female twins. Bioinformatics analyses of the associated methylation signals showed enrichment for neurological pathways in CWP.

Cited by 32 publications

References 56 publications

Genetic and epigenetic epidemiology of chronic widespread pain

Genetic and epigenetic epidemiology of chronic widespread pain

Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways

Association between Neuropathic Pain Characteristics and DNA Methylation of <em>TRPA1</em> in Human Peripheral Blood

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