title: Lack of validation of variants associated with cervical dystonia risk: a GWAS replication study.
abstract: BACKGROUND
  A recent genome-wide association study (GWAS) has identified a putative association, not statistically confirmed, of cervical dystonia within several regions in a British population. Hence, the authors proposed dysfunction of the ion channel NALCN (for sodium leak channel, nonselective) as a plausible cause of cervical dystonia. The objective of our study was to investigate the association of five single nucleotide polymorphisms (SNPs) previously reported with high signals as putative genetic risk factors for cervical dystonia in a British GWAS, including two located in the NALCN gene region.
  
  
  METHODS
  We performed a case-control association study in a Spanish population. The SNPs selected for genotyping were two SNPS in the NALCN gene (rs61973742 and rs1338041), one SNP in the OR4X2 gene (rs67863238), one SNP in the COL4A1 region (rs619152), and one intergenic SNP (rs1249277). Genomic DNA was collected from 252 patients with cervical dystonia, with a mean age of 55.3 ± 14.1 years (mean age at onset, 43.5 ± 15.7 years), and 342 unrelated control subjects with a mean age of 56.3 ± 14.3 years. Genotyping of SNPs was performed using TaqMan assays and SimpleProbe assays.
  
  
  RESULTS
  The SNP rs619152 had to be excluded because of assay failure. No significant differences were found in allele distribution between cases and controls for all analyzed SNPs. Therefore, we found no association with cervical dystonia for the analyzed SNPs in our Spanish population.
  
  
  CONCLUSIONS
  We did not find any evidence supporting the association of NALCN with cervical dystonia, indicating that this gene is not implicated in the pathogenesis of this disorder in our cervical dystonia population.
authors.affiliation: Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gómez-Garre
authors.forename: Ismael
authors.initials: I
authors.lastname: Huertas-Fernández
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Cáceres-Redondo
authors.forename: Araceli
authors.initials: A
authors.lastname: Alonso-Canovas
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Bernal-Bernal
authors.forename: Alberto
authors.initials: A
authors.lastname: Blanco-Ollero
authors.forename: Marta
authors.initials: M
authors.lastname: Bonilla-Toribio
authors.forename: Juan Andrés
authors.initials: JA
authors.lastname: Burguera
authors.forename: Manuel
authors.initials: M
authors.lastname: Carballo
authors.forename: Fatima
authors.initials: F
authors.lastname: Carrillo
authors.forename: M
authors.initials: M
authors.lastname: José Catalán-Alonso
authors.forename: Francisco
authors.initials: F
authors.lastname: Escamilla-Sevilla
authors.forename: Raul
authors.initials: R
authors.lastname: Espinosa-Rosso
authors.forename: María
authors.initials: M
authors.lastname: Carmen Fernández-Moreno
authors.forename: Juan
authors.initials: J
authors.lastname: García-Caldentey
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-Moreno
authors.forename: Sandra
authors.initials: S
authors.lastname: Giacometti-Silveira
authors.forename: Javier
authors.initials: J
authors.lastname: Gutiérrez-García
authors.forename: Silvia
authors.initials: S
authors.lastname: Jesús-Maestre
authors.forename: Eva
authors.initials: E
authors.lastname: López-Valdés
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Martínez-Castrillo
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Medialdea-Natera
authors.forename: Carolina
authors.initials: C
authors.lastname: Méndez-Lucena
authors.forename: Adolfo
authors.initials: A
authors.lastname: Mínguez-Castellanos
authors.forename: Miguel
authors.initials: M
authors.lastname: Angel Moya
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Ochoa-Sepulveda
authors.forename: Tomas
authors.initials: T
authors.lastname: Ojea
authors.forename: Nuria
authors.initials: N
authors.lastname: Rodríguez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rubio-Agusti
authors.forename: Miriam
authors.initials: M
authors.lastname: Sillero-Sánchez
authors.forename: Javier
authors.initials: J
authors.lastname: Del Val
authors.forename: Laura
authors.initials: L
authors.lastname: Vargas-González
authors.forename: Pablo
authors.initials: P
authors.lastname: Mir
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D004421:Dystonia / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D044465:White People
keywords: GWAS; association study; cervical dystonia; primary dystonia; replication