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Genome-wide association study in musician's dystonia: A risk variant at the arylsulfatase G locus?

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  • Funding agencies: This study was supported by the German Research Foundation (DFG) (LO1555/4-1; ZI591/18-1), the Volkswagen Foundation, and the Hermann and Lilly Schilling Foundation.

  • Relevant conflicts of interest/financial disclosures: Marina A.J. Tijssen is supported by the Prinses Beatrix Fund and the wetenschapsfonds Dutch dystonievereniging. Pilar Gómez-Garre and Pablo Mir receive grants from the Ministerio de Economía y Competitividad de España (SAF2007–60700); the Instituto de Salud Carlos III (PI10/01674, CP08/00174), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0377/2007, PI-0741/2010, PI-0437–2012), the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, and the Fundación Alicia Koplowitz. Pilar Gómez-Garre is funded by the “Miguel Servet” program from the Instituto de Salud Carlos III. Vladimir S. Kostic and Marina Svetel are supported by the Ministry of Education and Science, Republic of Serbia (# 145090). Enza Maria Valente is supported by the Italian Ministry of Health.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Musician's dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument. Little is known about genetic risk factors, although MD or writer's dystonia (WD) occurs in relatives of 20% of MD patients. We conducted a 2-stage genome-wide association study in whites. Genotypes at 557,620 single-nucleotide polymorphisms (SNPs) passed stringent quality control for 127 patients and 984 controls. Ten SNPs revealed P < 10−5 and entered the replication phase including 116 MD patients and 125 healthy musicians. A genome-wide significant SNP (P < 5 × 10−8) was also genotyped in 208 German or Dutch WD patients, 1,969 Caucasian, Spanish, and Japanese patients with other forms of focal or segmental dystonia as well as in 2,233 ethnically matched controls. Genome-wide significance with MD was observed for an intronic variant in the arylsulfatase G (ARSG) gene (rs11655081; P = 3.95 × 10−9; odds ratio [OR], 4.33; 95% confidence interval [CI], 2.66-7.05). rs11655081 was also associated with WD (P = 2.78 × 10−2) but not with any other focal or segmental dystonia. The allele frequency of rs11655081 varies substantially between different populations. The population stratification in our sample was modest (λ = 1.07), but the effect size may be overestimated. Using a small but homogenous patient sample, we provide data for a possible association of ARSG with MD. The variant may also contribute to the risk of WD, a form of dystonia that is often found in relatives of MD patients. © 2013 International Parkinson and Movement Disorder Society

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