Literature DB >> 25256078

Lack of validation of variants associated with cervical dystonia risk: a GWAS replication study.

Pilar Gómez-Garre1, Ismael Huertas-Fernández, María Teresa Cáceres-Redondo, Araceli Alonso-Canovas, Inmaculada Bernal-Bernal, Alberto Blanco-Ollero, Marta Bonilla-Toribio, Juan Andrés Burguera, Manuel Carballo, Fatima Carrillo, M José Catalán-Alonso, Francisco Escamilla-Sevilla, Raul Espinosa-Rosso, María Carmen Fernández-Moreno, Juan García-Caldentey, José Manuel García-Moreno, Sandra Giacometti-Silveira, Javier Gutiérrez-García, Silvia Jesús-Maestre, Eva López-Valdés, Juan Carlos Martínez-Castrillo, María Pilar Medialdea-Natera, Carolina Méndez-Lucena, Adolfo Mínguez-Castellanos, Miguel Angel Moya, Juan José Ochoa-Sepulveda, Tomas Ojea, Nuria Rodríguez, Ignacio Rubio-Agusti, Miriam Sillero-Sánchez, Javier Del Val, Laura Vargas-González, Pablo Mir.   

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.
© 2014 International Parkinson and Movement Disorder Society.

Entities:  

Keywords:  GWAS; association study; cervical dystonia; primary dystonia; replication

Mesh:

Year:  2014        PMID: 25256078     DOI: 10.1002/mds.26044

Source DB:  PubMed          Journal:  Mov Disord        ISSN: 0885-3185            Impact factor:   10.338


  8 in total

Review 1.  Defining research priorities in dystonia.

Authors:  Codrin Lungu; Laurie Ozelius; David Standaert; Mark Hallett; Beth-Anne Sieber; Christine Swanson-Fisher; Brian D Berman; Nicole Calakos; Jennifer C Moore; Joel S Perlmutter; Sarah E Pirio Richardson; Rachel Saunders-Pullman; Laura Scheinfeldt; Nutan Sharma; Roy Sillitoe; Kristina Simonyan; Philip A Starr; Anna Taylor; Jerrold Vitek
Journal:  Neurology       Date:  2020-02-25       Impact factor: 9.910

2.  Polygenic Risk of Spasmodic Dysphonia is Associated With Vulnerable Sensorimotor Connectivity.

Authors:  Gregory Garbès Putzel; Giovanni Battistella; Anna F Rumbach; Laurie J Ozelius; Mert R Sabuncu; Kristina Simonyan
Journal:  Cereb Cortex       Date:  2018-01-01       Impact factor: 5.357

Review 3.  Isolated dystonia: clinical and genetic updates.

Authors:  Aloysius Domingo; Rachita Yadav; Laurie J Ozelius
Journal:  J Neural Transm (Vienna)       Date:  2020-11-27       Impact factor: 3.575

4.  Association Analysis of NALCN Polymorphisms rs1338041 and rs61973742 in a Chinese Population with Isolated Cervical Dystonia.

Authors:  Qingqing Zhou; Jing Yang; Bei Cao; Yongping Chen; Qianqian Wei; Ruwei Ou; Wei Song; Bi Zhao; Ying Wu; Huifang Shang
Journal:  Parkinsons Dis       Date:  2016-04-28

Review 5.  Unmet Needs in Dystonia: Genetics and Molecular Biology-How Many Dystonias?

Authors:  Dineke S Verbeek; Thomas Gasser
Journal:  Front Neurol       Date:  2017-01-16       Impact factor: 4.003

6.  A Multi-center Genome-wide Association Study of Cervical Dystonia.

Authors:  Yan V Sun; Chengchen Li; Qin Hui; Yunfeng Huang; Richard Barbano; Ramon Rodriguez; Irene A Malaty; Stephen Reich; Kimberly Bambarger; Katie Holmes; Joseph Jankovic; Neepa J Patel; Emmanuel Roze; Marie Vidailhet; Brian D Berman; Mark S LeDoux; Alberto J Espay; Pinky Agarwal; Sarah Pirio-Richardson; Samuel A Frank; William G Ondo; Rachel Saunders-Pullman; Sylvain Chouinard; Stover Natividad; Alfredo Berardelli; Alexander Y Pantelyat; Allison Brashear; Susan H Fox; Meike Kasten; Ulrike M Krämer; Miriam Neis; Tobias Bäumer; Sebastian Loens; Max Borsche; Simone Zittel; Antonia Maurer; Mathias Gelderblom; Jens Volkmann; Thorsten Odorfer; Andrea A Kühn; Friederike Borngräber; Inke R König; Carlos Cruchaga; Adam C Cotton; Gamze Kilic-Berkmen; Alan Freeman; Stewart A Factor; Laura Scorr; J Douglas Bremner; Viola Vaccarino; Arshed A Quyyumi; Christine Klein; Joel S Perlmutter; Katja Lohmann; Hyder A Jinnah
Journal:  Mov Disord       Date:  2021-07-28       Impact factor: 10.338

Review 7.  Risk Factor Genes in Patients with Dystonia: A Comprehensive Review.

Authors:  Vasileios Siokas; Athina-Maria Aloizou; Zisis Tsouris; Amalia Michalopoulou; Alexios-Fotios A Mentis; Efthimios Dardiotis
Journal:  Tremor Other Hyperkinet Mov (N Y)       Date:  2019-01-09

8.  Association Between Dystonia-Related Genetic Loci and Parkinson's Disease in Eastern China.

Authors:  Wen-Yi Yang; Si-Si Jiang; Jia-Li Pu; Chong-Yao Jin; Ting Gao; Ran Zheng; Jun Tian; Bao-Rong Zhang
Journal:  Front Neurol       Date:  2022-02-22       Impact factor: 4.003

  8 in total

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