Abstract

Dystonia is a common movement disorder. A number of monogenic causes have been identified. However, the majority of dystonia cases are not explained by single gene defects. Cervical dystonia is one of the commonest forms without genetic causes identified. This pilot study aimed to identify large effect-size risk loci in cervical dystonia. A genomewide association study (GWAS) was performed. British resident cervical dystonia patients of European descent were genotyped using the Illumina-610-Quad. Comparison was made with controls of European descent from the Wellcome Trust Case Control Consortium using logistic regression algorithm from PLINK. SNPs not genotyped by the array were imputed with 1000 Genomes Project data using the MaCH algorithm and minimac. Postimputation analysis was done with the mach2dat algorithm using a logistic regression model. After quality control measures, 212 cases were compared with 5173 controls. No single SNP passed the genomewide significant level of 5 × 10(-8) in the analysis of genotyped SNP in PLINK. Postimputation, there were 5 clusters of SNPs that had P value <5 × 10(-6) , and the best cluster of SNPs was found near exon 1 of NALCN, (sodium leak channel) with P = 9.76 × 10(-7) . Several potential regions were found in the GWAS and imputation analysis. The lowest P value was found in NALCN. Dysfunction of this ion channel is a plausible cause for dystonia. Further replication in another cohort is needed to confirm this finding. We make this data publicly available to encourage further analyses of this disorder.