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

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 environment...

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Autores principales: Livshits, Gregory, Malkin, Ida, Bowyer, Ruth C.E., Verdi, Serena, Bell, Jordana T., Menni, Cristina, Williams, Frances M.K., Steves, Claire J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250282/
https://www.ncbi.nlm.nih.gov/pubmed/30086113
http://dx.doi.org/10.1097/j.pain.0000000000001364
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author Livshits, Gregory
Malkin, Ida
Bowyer, Ruth C.E.
Verdi, Serena
Bell, Jordana T.
Menni, Cristina
Williams, Frances M.K.
Steves, Claire J.
author_facet Livshits, Gregory
Malkin, Ida
Bowyer, Ruth C.E.
Verdi, Serena
Bell, Jordana T.
Menni, Cristina
Williams, Frances M.K.
Steves, Claire J.
author_sort Livshits, Gregory
collection PubMed
description 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.
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spelling pubmed-62502822018-12-10 Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways Livshits, Gregory Malkin, Ida Bowyer, Ruth C.E. Verdi, Serena Bell, Jordana T. Menni, Cristina Williams, Frances M.K. Steves, Claire J. Pain Research Paper 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. Wolters Kluwer 2018-10-25 2018-12 /pmc/articles/PMC6250282/ /pubmed/30086113 http://dx.doi.org/10.1097/j.pain.0000000000001364 Text en Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Livshits, Gregory
Malkin, Ida
Bowyer, Ruth C.E.
Verdi, Serena
Bell, Jordana T.
Menni, Cristina
Williams, Frances M.K.
Steves, Claire J.
Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways
title Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways
title_full Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways
title_fullStr Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways
title_full_unstemmed Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways
title_short Multi-OMICS analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways
title_sort multi-omics analyses of frailty and chronic widespread musculoskeletal pain suggest involvement of shared neurological pathways
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250282/
https://www.ncbi.nlm.nih.gov/pubmed/30086113
http://dx.doi.org/10.1097/j.pain.0000000000001364
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