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An omics investigation into chronic widespread musculoskeletal pain reveals epiandrosterone sulfate as a potential biomarker.

ABSTRACT: Chronic widespread musculoskeletal pain (CWP) is common, having a population prevalence of 10%. This study aimed to define the biological basis of the CWP/body mass association by using a systems biology approach. Adult female twins (n = 2444) from the TwinsUK registry who had extensive clinical, anthropometric, and "omic" data were included. Nontargeted metabolomics screening including 324 metabolites was carried out for CWP and body composition using dual-energy X-ray absorptiometry. The biological basis of these associations was explored through a genome-wide association study and replicated in an independent population sample (Cooperative Health Research in the Region of Augsburg [KORA] study, n = 2483). A causal role for the genetic variants identified was sought in CWP using a Mendelian randomisation study design. Fat mass/height2 was the body composition variable most strongly associated with CWP (TwinsUK: P = 2.4 × 10(-15) and KORA: P = 1.59 × 10(-10)). Of 324 metabolites examined, epiandrosterone sulfate (EAS) was highly associated with both CWP (P = 1.05 × 10(-09) in TwinsUK and P = 3.70 × 10(-06) in KORA) and fat mass/height2. Genome-wide association study of EAS identified imputed single nucleotide polymorphism rs1581492 at 7q22.1 to be strikingly associated with EAS levels (P ? 2.49 × 10(-78)), and this result was replicated in KORA (P = 2.12 × 10(-9)). Mendelian randomization by rs1581492 genotype showed that EAS is unlikely to be causally related to CWP. Using an agnostic omics approach to focus on the association of CWP with body mass index, we have confirmed a steroid hormone association and identified a genetic variant upstream of the CYP genes, which likely controls this response. This study suggests that steroid hormone abnormalities result from pain rather than causing it, and EAS may provide a biomarker that identifies subgroups at risk of CWP.

SUBMITTER: Livshits G

PROVIDER: S-EPMC4770329 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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An omics investigation into chronic widespread musculoskeletal pain reveals epiandrosterone sulfate as a potential biomarker.

Livshits Gregory G Macgregor Alexander J AJ Gieger Christian C Malkin Ida I Moayyeri Alireza A Grallert Harald H Emeny Rebecca T RT Spector Tim T Kastenmüller Gabi G Williams Frances M K FMK

Pain 20151001 10

Chronic widespread musculoskeletal pain (CWP) is common, having a population prevalence of 10%. This study aimed to define the biological basis of the CWP/body mass association by using a systems biology approach. Adult female twins (n = 2444) from the TwinsUK registry who had extensive clinical, anthropometric, and "omic" data were included. Nontargeted metabolomics screening including 324 metabolites was carried out for CWP and body composition using dual-energy X-ray absorptiometry. The biolo ...[more]

PMID: 25915148

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Project description:ImportanceTick-borne diseases (TBDs) other than Lyme disease, such as spotted fever group rickettsiosis, ehrlichiosis, and galactose-α-1,3-galactose (α-gal) syndrome, are an emerging public health issue. Long-term sequelae secondary to Ehrlichia or Rickettsia infection are uncommon; however, musculoskeletal symptoms are often attributed to prior tick exposure.ObjectiveTo evaluate the potential associations between prior exposure to TBDs and musculoskeletal symptoms, including radiographic osteoarthritis.Design, setting, and participantsThis cross-sectional study analyzed serum samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing longitudinal, population-based study in Johnston County, North Carolina. Biospecimen testing and analysis were performed between May 2022 and November 2023. Participants in the JoCo OA project are noninstitutionalized White and Black Johnston County residents 45 years or older.Main outcome and measuresThe primary outcome was seropositivity with Ehrlichia IgG, Rickettsia IgG, and/or α-gal IgE and musculoskeletal symptoms. Secondary outcomes included risk factors associated with elevated α-gal IgE and weighted population point prevalence rates. Participants completed questionnaires, underwent physical assessments, and provided biospecimens for serological testing. Multivariable models were used to estimate associations of interest.ResultsOf the 605 participants who completed the fourth visit of the JoCo OA project, 488 (80.7%) had serum samples available for testing. The 488 participants had a median (IQR) age of 72 (68-78) years and included 336 females (68.9%) and 161 Black (33.0%) and 327 White (67.0%) individuals. The overall weighted point prevalence was 8.6% (95% CI, 5.9%-11.3%) for Ehrlichia IgG, 17.1% (95% CI, 12.6%-21.5%) for Rickettsia IgG, and 19.6% (95% CI, 15.3%-23.8%) for α-gal IgE level greater than 0.1 IU/mL. Only α-gal IgE was associated with knee pain, aching or stiffness (mean ratio, 1.30; 95% CI, 1.09-1.56). Antibodies to Rickettsia, Ehrlichia, and α-gal were not associated with symptomatic radiographic knee osteoarthritis. Male sex (odds ratio [OR], 2.63; 95% CI, 1.55-4.47), current smoker status (OR, 3.55; 95% CI, 1.38-9.18), and an attached tick bite in the past 5 years (OR, 3.99; 95% CI, 2.22-7.15) were all risk factors that were associated with α-gal IgE level greater than 0.1 IU/mL. Despite only 84 individuals (17.2%) recalling a tick bite in the past 5 years, 178 (36.5%) had evidence of prior tick-borne exposure, suggesting frequent human-tick interactions.Conclusions and relevanceResults of this cross-sectional study indicate no association between Ehrlichia or Rickettsia seropositivity and chronic musculoskeletal symptoms or osteoarthritis. Further investigation is needed into the pathogenesis of α-gal syndrome and interventions to reduce human-tick interactions.

Project description:BACKGROUND:Chronic musculoskeletal pain (MSP) is frequent in adolescents and has major medical and social consequences. In many cases, when no cause has been clearly established, this pain may be considered to be chronic idiopathic MSP. Our study seeks to identify general criteria for this type of pain through the experience of professionals from tertiary care centers with expertise in pediatric and adolescent chronic MSP. METHODS:Cross-sectional multicenter qualitative study. Semi-structured interviews of 25 professionals at a rheumatology reference center and in its network for pain management, including diverse specialists and professions. Interpretative Phenomenological Analysis is used to explore the data. RESULTS:This approach led us to identify 10 themes organized around three superordinate themes covering different stages of the diagnostic process: 1) the medical pain history up to the consultation at the reference center; 2) the professional's subjective feelings about the clinical presentation; 3) from the clinical examination to diagnosis and treatment of chronic idiopathic MSP. The main elements guiding this diagnosis do not come from the physical examination but from the medical history and the professionals' subjective feelings, that is, their clinical judgment. The professionals' impression of uneasiness and frustration, induced by patients and their parents, is of major importance. CONCLUSION:The principal elements guiding the diagnosis of chronic idiopathic MSP do not come primarily from the physical examination but rather from the pain history and the health professional's subjective feelings. Our results suggest that the concept of Juvenile Fibromyalgia (JFM) does not appear to cover all situations of chronic idiopathic MSP in adolescence. A constellation of non-organic criteria enables diagnosis of the latter; these criteria should be validated to avoid medical nomadism and multiple investigations and to shorten the interval until patients receive optimal pain management. CLINICAL TRIAL REGISTRATION:clinicaltrials.gov, NCT03171792, https://clinicaltrials.gov/ct2/show/NCT03171792?term=LACHAL&cntry=FR&city=paris&rank=1.

Dataset Information

An omics investigation into chronic widespread musculoskeletal pain reveals epiandrosterone sulfate as a potential biomarker.

Publications

An omics investigation into chronic widespread musculoskeletal pain reveals epiandrosterone sulfate as a potential biomarker.

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