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

Elisa Docampo, Georgia Escaramís, Mònica Gratacòs, Sergi Villatoro, Anna Puig, Manolis Kogevinas, Antonio Collado, Jordi Carbonell, Javier Rivera, Javier Vidal, Jose Alegre, Xavier Estivill, Raquel Rabionet

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26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1102-1109
Number of pages8
JournalPain
Volume155
Issue number6
DOIs
Publication statusPublished - Jun 2014

Keywords

  • CNV
  • Copy number variants
  • Fibromyalgia
  • GWAS
  • Genome-wide association scan
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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    Docampo, E., Escaramís, G., Gratacòs, M., Villatoro, S., Puig, A., Kogevinas, M., Collado, A., Carbonell, J., Rivera, J., Vidal, J., Alegre, J., Estivill, X., & Rabionet, R. (2014). Genome-wide analysis of single nucleotide polymorphisms and copy number variants in fibromyalgia suggest a role for the central nervous system. Pain, 155(6), 1102-1109. https://doi.org/10.1016/j.pain.2014.02.016