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Genome‐wide association study in musician's dystonia: A risk variant at the arylsulfatase G locus?
Author(s) -
Lohmann Katja,
Schmidt Alexander,
Schillert Arne,
Winkler Susen,
Albanese Alberto,
Baas Frank,
Bentivoglio Anna Rita,
Borngräber Friederike,
Brüggemann Norbert,
Defazio Giovanni,
Del Sorbo Francesca,
Deuschl Günther,
Edwards Mark J.,
Gasser Thomas,
GómezGarre Pilar,
Graf Julia,
Groen Justus L.,
Grünewald Anne,
Hagenah Johann,
Hemmelmann Claudia,
Jabusch HansChristian,
Kaji Ryuji,
Kasten Meike,
Kawakami Hideshi,
Kostic Vladimir S.,
Liguori Maria,
Mir Pablo,
Münchau Alexander,
Ricchiuti Felicia,
Schreiber Stefan,
Siegesmund Katharina,
Svetel Marina,
Tijssen Marina A.J.,
Valente Enza Maria,
Westenberger Ana,
Zeuner Kirsten E.,
Zittel Simone,
Altenmüller Eckart,
Ziegler Andreas,
Klein Christine
Publication year - 2014
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.25791
Subject(s) - single nucleotide polymorphism , odds ratio , dystonia , population stratification , case control study , genetics , genome wide association study , snp , allele frequency , confidence interval , population , allele , locus (genetics) , medicine , genotype , biology , psychology , gene , psychiatry , environmental health
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