title: Genome-wide association study in musician's dystonia: a risk variant at the arylsulfatase G locus?
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.
authors.affiliation: Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Lohmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.forename: Arne
authors.initials: A
authors.lastname: Schillert
authors.forename: Susen
authors.initials: S
authors.lastname: Winkler
authors.forename: Alberto
authors.initials: A
authors.lastname: Albanese
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bentivoglio
authors.forename: Friederike
authors.initials: F
authors.lastname: Borngräber
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.forename: Giovanni
authors.initials: G
authors.lastname: Defazio
authors.forename: Francesca
authors.initials: F
authors.lastname: Del Sorbo
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.forename: Pilar
authors.initials: P
authors.lastname: Gómez-Garre
authors.forename: Julia
authors.initials: J
authors.lastname: Graf
authors.forename: Justus L
authors.initials: JL
authors.lastname: Groen
authors.forename: Anne
authors.initials: A
authors.lastname: Grünewald
authors.forename: Johann
authors.initials: J
authors.lastname: Hagenah
authors.forename: Claudia
authors.initials: C
authors.lastname: Hemmelmann
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Jabusch
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
authors.forename: Meike
authors.initials: M
authors.lastname: Kasten
authors.forename: Hideshi
authors.initials: H
authors.lastname: Kawakami
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostic
authors.forename: Maria
authors.initials: M
authors.lastname: Liguori
authors.forename: Pablo
authors.initials: P
authors.lastname: Mir
authors.forename: Alexander
authors.initials: A
authors.lastname: Münchau
authors.forename: Felicia
authors.initials: F
authors.lastname: Ricchiuti
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Katharina
authors.initials: K
authors.lastname: Siegesmund
authors.forename: Marina
authors.initials: M
authors.lastname: Svetel
authors.forename: Marina A J
authors.initials: MA
authors.lastname: Tijssen
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Ana
authors.initials: A
authors.lastname: Westenberger
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Zeuner
authors.forename: Simone
authors.initials: S
authors.lastname: Zittel
authors.forename: Eckart
authors.initials: E
authors.lastname: Altenmüller
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
mesh_terms: D001192:Arylsulfatases / Q000235:genetics*; D020821:Dystonic Disorders / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D055106:Genome-Wide Association Study; D006801:Humans; D011597:Psychomotor Performance / Q000502:physiology*; D012306:Risk; D012307:Risk Factors
chemical_list: C476553:ARSG protein, human; D001192:Arylsulfatases
keywords: association study; dystonia; risk factor; sulfatase