ArticlePain2018
Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways.
Article in Pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The Metabolomics of Chronic Pain Conditions: A Systematic Review.Biological research for nursing · 2020Pooled it
- Article
- Frailty Transition and Risk of New-Onset Arthritis Among Adults Aged 45 Years and Older: A Longitudinal Analysis of CHARLS.Healthcare (Basel, Switzerland) · 2026Article
- Metabolomic sweet spot clock predicts mortality and age-related diseases in the Canadian Longitudinal Study on Aging.Communications medicine · 2026Article
- Exploring salivary metabolites as biomarkers in chronic craniofacial and orofacial pain: a metabolomic analysis.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Integrating brain proteomes and genetics to identify novel risk genes in chronic widespread musculoskeletal pain.Scientific reports · 2025Article
- Delineating Life-Course Percentile Curves and Normative Values of Multi-Systemic Ageing Metrics in the United Kingdom, the United States, and China.Journal of cachexia, sarcopenia and muscle · 2025Article
- 1H-NMR-based metabolomics identifies disrupted betaine metabolism as distinct serum signature of pre-frailty.npj aging · 2025Article
- Salivary Metabolomics as a Diagnostic Tool: Distinct Metabolic Profiles Across Orofacial Pain Subtypes.International journal of molecular sciences · 2025Article
- Innovations in acute and chronic pain biomarkers: enhancing diagnosis and personalized therapy.Regional anesthesia and pain medicine · 2025Review
- Article
- Exploring the metabolomics profile of frailty- a systematic review.Journal of diabetes and metabolic disorders · 2024Review
- Article
- Validation of a polygenic risk score for frailty in the Lothian Birth Cohort 1936 and English longitudinal study of ageing.Scientific reports · 2024Article
- The intersection of frailty and metabolism.Cell metabolism · 2024Review
- Metabolites in aging and aging-relevant diseases: Frailty, sarcopenia and cognitive decline.Geriatrics & gerontology international · 2024Review
- The vicious cycle of frailty and pain: a two-sided causal relationship revealed.Frontiers in medicine · 2024Article
- Exploring causality between bone mineral density and frailty: A bidirectional Mendelian randomization study.PloS one · 2024Article
- Article
- Genetic and Environmental Influences on Longitudinal Frailty Trajectories From Adulthood into Old Age.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Chronic widespread musculoskeletal pain (CWP) and frailty are prevalent conditions in older people. We have shown previously that interindividual variation in frailty and CWP is genetically determined. We also reported an association of frailty and CWP caused by shared genetic and common environmental factors. The aim of this study was to use omic approaches to identify molecular genetic factors underlying the heritability of frailty and its genetic correlation with CWP. Frailty was quantified through the Rockwood Frailty Index (FI) as a proportion of deficits from 33 binary health deficit questions in 3626 female twins. Common widespread pain was assessed using a screening questionnaire. OMICS analysis included 305 metabolites and whole-genome (>2.5 × 10 SNPs) and epigenome (∼1 × 10 MeDIP-seq regions) assessments performed on fasting blood samples. Using family-based statistical analyses, including path analysis, we examined how FI scores were related to molecular genetic factors and to CWP, taking into account known risk factors such as fat mass and smoking. Frailty Index was significantly correlated with 51 metabolites after correction for multiple testing, with 20 metabolites having P-values between 2.1 × 10 and 4.0 × 10. Three metabolites (uridine, C-glycosyl tryptophan, and N-acetyl glycine) were statistically independent and thought to exert a direct effect on FI. Epiandrosterone sulphate, previously shown to be highly inversely associated with CWP, was found to exert an indirect influence on FI. Bioinformatics analysis of genome-wide association study and EWAS showed that FI and its covariation with CWP was through genomic regions involved in neurological pathways. Neurological pathway involvement accounts for the associated conditions of aging CWP and FI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.