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  • Bell, Jordana T.  (3)
  • Williams, Frances M.K.  (3)
  • English  (3)
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  • English  (3)
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  • 1
    Online Resource
    Online Resource
    Genome-wide methylation analysis of a large population sample shows neurological pathways involvement in chronic widespread musculoskeletal pain
    Index Copernicus ; 2018
    In:  BÓL Vol. 19, No. 1 ( 2018-6-30), p. 11-22
    Details
    In: BÓL, Index Copernicus, Vol. 19, No. 1 ( 2018-6-30), p. 11-22
    Abstract: Chronic widespread musculoskeletal pain (CWP), has a considerable heritable component, which remains to be explained. Epigenetic factors may contribute to and account for some of the heritability estimate. We analysed epigenome-wide methylation using MeDIPseq in whole blood DNA from 1708 monozygotic and dizygotic Caucasian twins having CWP prevalence of 19.9%. Longitudinally stable methylation bins (lsBINs), were established by testing repeated measurements conducted ≥3 years apart, n = 292. DNA methylation variation at lsBINs was tested for association with CWP in a discovery set of 50 monozygotic twin pairs discordant for CWP, and in an independent dataset (n = 1608 twins), and the results from the 2 samples were combined using Fisher method. Functional interpretation of the most associated signals was based on functional genomic annotations, gene ontology, and pathway analyses. Of 723,029 signals identified as IsBINs, 26,399 lsBINs demonstrated the same direction of association in both discovery and replication datasets at nominal significance (P ≤ 0.05). In the combined analysis across 1708 individuals, whereas no lsBINs showed genome-wide significance (P 〈 10-8), 24 signals reached p≤9E-5, and these included association signals mapping in or near to IL17A, ADIPOR2, and TNFRSF13B. Bioinformatics analyses of the associated methylation bins showed enrichment for neurological pathways in CWP. We estimate that the variance explained by epigenetic factors in CWP is 6%. This, the largest study to date of DNA methylation in CWP, points towards epigenetic modification of neurological pathways in CWP and provides proof of principle of this method in teasing apart the complex risk factors for CWP.
    Type of Medium: Online Resource
    ISSN: 1640-324X
    URL: Journal
    URL: Article
    DOI: 10.5604/1640324X
    DOI: 10.5604/01.3001.0012.5920
    Language: English
    Publisher: Index Copernicus
    Publication Date: 2018
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Genome-wide methylation analysis of a large population sample shows neurological pathways involvement in chronic widespread musculoskeletal pain
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Pain Vol. 158, No. 6 ( 2017-06), p. 1053-1062
    Details
    In: Pain, Ovid Technologies (Wolters Kluwer Health), Vol. 158, No. 6 ( 2017-06), p. 1053-1062
    Abstract: Chronic widespread musculoskeletal pain (CWP), has a considerable heritable component, which remains to be explained. Epigenetic factors may contribute to and account for some of the heritability estimate. We analysed epigenome-wide methylation using MeDIPseq in whole blood DNA from 1708 monozygotic and dizygotic Caucasian twins having CWP prevalence of 19.9%. Longitudinally stable methylation bins (lsBINs), were established by testing repeated measurements conducted ≥3 years apart, n = 292. DNA methylation variation at lsBINs was tested for association with CWP in a discovery set of 50 monozygotic twin pairs discordant for CWP, and in an independent dataset (n = 1608 twins), and the results from the 2 samples were combined using Fisher method. Functional interpretation of the most associated signals was based on functional genomic annotations, gene ontology, and pathway analyses. Of 723,029 signals identified as lsBINs, 26,399 lsBINs demonstrated the same direction of association in both discovery and replication datasets at nominal significance ( P ≤ 0.05). In the combined analysis across 1708 individuals, whereas no lsBINs showed genome-wide significance ( P 〈 10-8), 24 signals reached p≤9E-5, and these included association signals mapping in or near to IL17A , ADIPOR2, and TNFRSF13B . Bioinformatics analyses of the associated methylation bins showed enrichment for neurological pathways in CWP. We estimate that the variance explained by epigenetic factors in CWP is 6%. This, the largest study to date of DNA methylation in CWP, points towards epigenetic modification of neurological pathways in CWP and provides proof of principle of this method in teasing apart the complex risk factors for CWP.
    Type of Medium: Online Resource
    ISSN: 0304-3959 , 1872-6623
    URL: Article
    DOI: 10.1097/j.pain.0000000000000880
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1494115-6
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  • 3
    Online Resource
    Online Resource
    Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Pain Vol. 159, No. 12 ( 2018-12), p. 2565-2572
    Details
    In: Pain, Ovid Technologies (Wolters Kluwer Health), Vol. 159, No. 12 ( 2018-12), p. 2565-2572
    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 6 SNPs) and epigenome (∼1 × 10 6 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 −6 and 4.0 × 10 −16 . 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.
    Type of Medium: Online Resource
    ISSN: 0304-3959 , 1872-6623
    URL: Article
    DOI: 10.1097/j.pain.0000000000001364
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1494115-6
    Location Call Number Limitation Availability
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    Online Resource
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