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Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain

BACKGROUND AND OBJECTIVES: Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%–54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conduct...

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Autores principales: Rahman, Md Shafiqur, Winsvold, Bendik S, Chavez Chavez, Sergio O, Børte, Sigrid, Tsepilov, Yakov A, Sharapov, Sodbo Zh, Aulchenko, Yurii S, Hagen, Knut, Fors, Egil A, Hveem, Kristian, Zwart, John Anker, van Meurs, Joyce B, Freidin, Maxim B, Williams, Frances MK
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372387/
https://www.ncbi.nlm.nih.gov/pubmed/33926923
http://dx.doi.org/10.1136/annrheumdis-2020-219624
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author Rahman, Md Shafiqur
Winsvold, Bendik S
Chavez Chavez, Sergio O
Børte, Sigrid
Tsepilov, Yakov A
Sharapov, Sodbo Zh
Aulchenko, Yurii S
Hagen, Knut
Fors, Egil A
Hveem, Kristian
Zwart, John Anker
van Meurs, Joyce B
Freidin, Maxim B
Williams, Frances MK
author_facet Rahman, Md Shafiqur
Winsvold, Bendik S
Chavez Chavez, Sergio O
Børte, Sigrid
Tsepilov, Yakov A
Sharapov, Sodbo Zh
Aulchenko, Yurii S
Hagen, Knut
Fors, Egil A
Hveem, Kristian
Zwart, John Anker
van Meurs, Joyce B
Freidin, Maxim B
Williams, Frances MK
author_sort Rahman, Md Shafiqur
collection PubMed
description BACKGROUND AND OBJECTIVES: Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%–54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP. METHODS: Northern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined. RESULTS: Three genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes Ring Finger Protein 123 (RNF123), ATPase secretory pathway Ca (2+) transporting 1 (ATP2C1) and catechol-O-methyltransferase (COMT). The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227) and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP. CONCLUSIONS: We report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.
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spelling pubmed-83723872021-09-02 Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain Rahman, Md Shafiqur Winsvold, Bendik S Chavez Chavez, Sergio O Børte, Sigrid Tsepilov, Yakov A Sharapov, Sodbo Zh Aulchenko, Yurii S Hagen, Knut Fors, Egil A Hveem, Kristian Zwart, John Anker van Meurs, Joyce B Freidin, Maxim B Williams, Frances MK Ann Rheum Dis Pain BACKGROUND AND OBJECTIVES: Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%–54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP. METHODS: Northern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined. RESULTS: Three genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes Ring Finger Protein 123 (RNF123), ATPase secretory pathway Ca (2+) transporting 1 (ATP2C1) and catechol-O-methyltransferase (COMT). The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227) and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP. CONCLUSIONS: We report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis. BMJ Publishing Group 2021-09 2021-04-29 /pmc/articles/PMC8372387/ /pubmed/33926923 http://dx.doi.org/10.1136/annrheumdis-2020-219624 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
spellingShingle Pain
Rahman, Md Shafiqur
Winsvold, Bendik S
Chavez Chavez, Sergio O
Børte, Sigrid
Tsepilov, Yakov A
Sharapov, Sodbo Zh
Aulchenko, Yurii S
Hagen, Knut
Fors, Egil A
Hveem, Kristian
Zwart, John Anker
van Meurs, Joyce B
Freidin, Maxim B
Williams, Frances MK
Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain
title Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain
title_full Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain
title_fullStr Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain
title_full_unstemmed Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain
title_short Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain
title_sort genome-wide association study identifies rnf123 locus as associated with chronic widespread musculoskeletal pain
topic Pain
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372387/
https://www.ncbi.nlm.nih.gov/pubmed/33926923
http://dx.doi.org/10.1136/annrheumdis-2020-219624
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