Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system

Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we sele...

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Autores: Docampo Martínez, Elisa, Escaramís Babiano, Geòrgia, Gratacòs, Mònica, Villatoro, Sergi, Puig, Anna, Kogevinas, Manolis, Collado, Antonio, Carbonell, Jordi, Rivera, Javier, Vidal, Javier, Alegre, Jose, Estivill, Xavier, 1955-, Rabionet Janssen, Raquel
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2014
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/162420
Acceso en línea:https://hdl.handle.net/2445/162420
Access Level:acceso abierto
Palabra clave:Malalties del sistema nerviós central
Malalties rares
Central nervous system diseases
Rare diseases
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spelling Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous systemDocampo Martínez, ElisaEscaramís Babiano, GeòrgiaGratacòs, MònicaVillatoro, SergiPuig, AnnaKogevinas, ManolisCollado, AntonioCarbonell, JordiRivera, JavierVidal, JavierAlegre, JoseEstivill, Xavier, 1955-Rabionet Janssen, RaquelMalalties del sistema nerviós centralMalalties raresCentral nervous system diseasesRare diseasesFibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and we genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control women (Illumina 610k array) was obtained for genome-wide association scan (GWAS) analysis. Copy number variants in FM susceptibility were analyzed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2 × 400K platform. No single nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the most associated SNPs were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (P = 4.28 × 10−5, odds ratio [95% confidence interval] = 0.58 [0.44-0.75]). aCGH detected 5 differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 was demonstrated to be associated to female cases of FM with low levels of comorbidities (P = .021, odds ratio [95% confidence interval] = 1.46 [1.05-2.04]). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies, this would highlight a neurocognitive involvement in agreement with latest reports.Wolters Kluwer Health2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/162420Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1016/j.pain.2014.02.016Pain, 2014, vol. 155, num. 6, p. 1102-1109https://doi.org/10.1016/j.pain.2014.02.016(c) International Association for the Study of Pain, 2014info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1624202026-05-27T06:46:51Z
dc.title.none.fl_str_mv Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system
title Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system
spellingShingle Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system
Docampo Martínez, Elisa
Malalties del sistema nerviós central
Malalties rares
Central nervous system diseases
Rare diseases
title_short Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system
title_full Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system
title_fullStr Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system
title_full_unstemmed Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system
title_sort Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system
dc.creator.none.fl_str_mv Docampo Martínez, Elisa
Escaramís Babiano, Geòrgia
Gratacòs, Mònica
Villatoro, Sergi
Puig, Anna
Kogevinas, Manolis
Collado, Antonio
Carbonell, Jordi
Rivera, Javier
Vidal, Javier
Alegre, Jose
Estivill, Xavier, 1955-
Rabionet Janssen, Raquel
author Docampo Martínez, Elisa
author_facet Docampo Martínez, Elisa
Escaramís Babiano, Geòrgia
Gratacòs, Mònica
Villatoro, Sergi
Puig, Anna
Kogevinas, Manolis
Collado, Antonio
Carbonell, Jordi
Rivera, Javier
Vidal, Javier
Alegre, Jose
Estivill, Xavier, 1955-
Rabionet Janssen, Raquel
author_role author
author2 Escaramís Babiano, Geòrgia
Gratacòs, Mònica
Villatoro, Sergi
Puig, Anna
Kogevinas, Manolis
Collado, Antonio
Carbonell, Jordi
Rivera, Javier
Vidal, Javier
Alegre, Jose
Estivill, Xavier, 1955-
Rabionet Janssen, Raquel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties del sistema nerviós central
Malalties rares
Central nervous system diseases
Rare diseases
topic Malalties del sistema nerviós central
Malalties rares
Central nervous system diseases
Rare diseases
description Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and we genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control women (Illumina 610k array) was obtained for genome-wide association scan (GWAS) analysis. Copy number variants in FM susceptibility were analyzed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2 × 400K platform. No single nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the most associated SNPs were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (P = 4.28 × 10−5, odds ratio [95% confidence interval] = 0.58 [0.44-0.75]). aCGH detected 5 differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 was demonstrated to be associated to female cases of FM with low levels of comorbidities (P = .021, odds ratio [95% confidence interval] = 1.46 [1.05-2.04]). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies, this would highlight a neurocognitive involvement in agreement with latest reports.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/162420
url https://hdl.handle.net/2445/162420
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.pain.2014.02.016
Pain, 2014, vol. 155, num. 6, p. 1102-1109
https://doi.org/10.1016/j.pain.2014.02.016
dc.rights.none.fl_str_mv (c) International Association for the Study of Pain, 2014
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) International Association for the Study of Pain, 2014
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wolters Kluwer Health
publisher.none.fl_str_mv Wolters Kluwer Health
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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