Genome-wide association study in musician's dystonia: a risk variant at the arylsulfatase G locus?
Identifieur interne : 000568 ( Main/Exploration ); précédent : 000567; suivant : 000569Genome-wide association study in musician's dystonia: a risk variant at the arylsulfatase G locus?
Auteurs : Katja Lohmann [Allemagne] ; Alexander Schmidt ; Arne Schillert ; Susen Winkler ; Alberto Albanese ; Frank Baas ; Anna Rita Bentivoglio ; Friederike Borngr Ber ; Norbert Brüggemann ; Giovanni Defazio ; Francesca Del Sorbo ; Günther Deuschl ; Mark J. Edwards ; Thomas Gasser ; Pilar G Mez-Garre ; Julia Graf ; Justus L. Groen ; Anne Grünewald ; Johann Hagenah ; Claudia Hemmelmann ; Hans-Christian Jabusch ; Ryuji Kaji ; Meike Kasten ; Hideshi Kawakami ; Vladimir S. Kostic ; Maria Liguori ; Pablo Mir ; Alexander Münchau ; Felicia Ricchiuti ; Stefan Schreiber ; Katharina Siegesmund ; Marina Svetel ; Marina A J. Tijssen ; Enza Maria Valente ; Ana Westenberger ; Kirsten E. Zeuner ; Simone Zittel ; Eckart Altenmüller ; Andreas Ziegler ; Christine KleinSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2014.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Arylsulfatases.
- genetics : Dystonic Disorders.
- methods : Genetic Testing.
- physiology : Psychomotor Performance.
- Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Risk, Risk Factors.
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.
DOI: 10.1002/mds.25791
PubMed: 24375517
Affiliations:
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Edwards</name></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name></author><author><name sortKey="G Mez Garre, Pilar" sort="G Mez Garre, Pilar" uniqKey="G Mez Garre P" first="Pilar" last="G Mez-Garre">Pilar G Mez-Garre</name></author><author><name sortKey="Graf, Julia" sort="Graf, Julia" uniqKey="Graf J" first="Julia" last="Graf">Julia Graf</name></author><author><name sortKey="Groen, Justus L" sort="Groen, Justus L" uniqKey="Groen J" first="Justus L" last="Groen">Justus L. Groen</name></author><author><name sortKey="Grunewald, Anne" sort="Grunewald, Anne" uniqKey="Grunewald A" first="Anne" last="Grünewald">Anne Grünewald</name></author><author><name sortKey="Hagenah, Johann" sort="Hagenah, Johann" uniqKey="Hagenah J" first="Johann" last="Hagenah">Johann Hagenah</name></author><author><name sortKey="Hemmelmann, Claudia" sort="Hemmelmann, Claudia" uniqKey="Hemmelmann C" first="Claudia" last="Hemmelmann">Claudia Hemmelmann</name></author><author><name sortKey="Jabusch, Hans Christian" sort="Jabusch, Hans Christian" uniqKey="Jabusch H" first="Hans-Christian" last="Jabusch">Hans-Christian Jabusch</name></author><author><name sortKey="Kaji, Ryuji" sort="Kaji, Ryuji" uniqKey="Kaji R" first="Ryuji" last="Kaji">Ryuji Kaji</name></author><author><name sortKey="Kasten, Meike" sort="Kasten, Meike" uniqKey="Kasten M" first="Meike" last="Kasten">Meike Kasten</name></author><author><name sortKey="Kawakami, Hideshi" sort="Kawakami, Hideshi" uniqKey="Kawakami H" first="Hideshi" last="Kawakami">Hideshi Kawakami</name></author><author><name sortKey="Kostic, Vladimir S" sort="Kostic, Vladimir S" uniqKey="Kostic V" first="Vladimir S" last="Kostic">Vladimir S. Kostic</name></author><author><name sortKey="Liguori, Maria" sort="Liguori, Maria" uniqKey="Liguori M" first="Maria" last="Liguori">Maria Liguori</name></author><author><name sortKey="Mir, Pablo" sort="Mir, Pablo" uniqKey="Mir P" first="Pablo" last="Mir">Pablo Mir</name></author><author><name sortKey="Munchau, Alexander" sort="Munchau, Alexander" uniqKey="Munchau A" first="Alexander" last="Münchau">Alexander Münchau</name></author><author><name sortKey="Ricchiuti, Felicia" sort="Ricchiuti, Felicia" uniqKey="Ricchiuti F" first="Felicia" last="Ricchiuti">Felicia Ricchiuti</name></author><author><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name></author><author><name sortKey="Siegesmund, Katharina" sort="Siegesmund, Katharina" uniqKey="Siegesmund K" first="Katharina" last="Siegesmund">Katharina Siegesmund</name></author><author><name sortKey="Svetel, Marina" sort="Svetel, Marina" uniqKey="Svetel M" first="Marina" last="Svetel">Marina Svetel</name></author><author><name sortKey="Tijssen, Marina A J" sort="Tijssen, Marina A J" uniqKey="Tijssen M" first="Marina A J" last="Tijssen">Marina A J. Tijssen</name></author><author><name sortKey="Valente, Enza Maria" sort="Valente, Enza Maria" uniqKey="Valente E" first="Enza Maria" last="Valente">Enza Maria Valente</name></author><author><name sortKey="Westenberger, Ana" sort="Westenberger, Ana" uniqKey="Westenberger A" first="Ana" last="Westenberger">Ana Westenberger</name></author><author><name sortKey="Zeuner, Kirsten E" sort="Zeuner, Kirsten E" uniqKey="Zeuner K" first="Kirsten E" last="Zeuner">Kirsten E. Zeuner</name></author><author><name sortKey="Zittel, Simone" sort="Zittel, Simone" uniqKey="Zittel S" first="Simone" last="Zittel">Simone Zittel</name></author><author><name sortKey="Altenmuller, Eckart" sort="Altenmuller, Eckart" uniqKey="Altenmuller E" first="Eckart" last="Altenmüller">Eckart Altenmüller</name></author><author><name sortKey="Ziegler, Andreas" sort="Ziegler, Andreas" uniqKey="Ziegler A" first="Andreas" last="Ziegler">Andreas Ziegler</name></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Arylsulfatases (genetics)</term><term>Dystonic Disorders (genetics)</term><term>Genetic Loci</term><term>Genetic Predisposition to Disease</term><term>Genetic Testing (methods)</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Psychomotor Performance (physiology)</term><term>Risk</term><term>Risk Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Arylsulfatases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Dystonic Disorders</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genetic Testing</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Psychomotor Performance</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Genetic Loci</term><term>Genetic Predisposition to Disease</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Risk</term><term>Risk Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country></list><tree><noCountry><name sortKey="Albanese, Alberto" sort="Albanese, Alberto" uniqKey="Albanese A" first="Alberto" last="Albanese">Alberto Albanese</name><name sortKey="Altenmuller, Eckart" sort="Altenmuller, Eckart" uniqKey="Altenmuller E" first="Eckart" last="Altenmüller">Eckart Altenmüller</name><name sortKey="Baas, Frank" sort="Baas, Frank" uniqKey="Baas F" first="Frank" last="Baas">Frank Baas</name><name sortKey="Bentivoglio, Anna Rita" sort="Bentivoglio, Anna Rita" uniqKey="Bentivoglio A" first="Anna Rita" last="Bentivoglio">Anna Rita Bentivoglio</name><name sortKey="Borngr Ber, Friederike" sort="Borngr Ber, Friederike" uniqKey="Borngr Ber F" first="Friederike" last="Borngr Ber">Friederike Borngr Ber</name><name sortKey="Bruggemann, Norbert" sort="Bruggemann, Norbert" uniqKey="Bruggemann N" first="Norbert" last="Brüggemann">Norbert Brüggemann</name><name sortKey="Defazio, Giovanni" sort="Defazio, Giovanni" uniqKey="Defazio G" first="Giovanni" last="Defazio">Giovanni Defazio</name><name sortKey="Del Sorbo, Francesca" sort="Del Sorbo, Francesca" uniqKey="Del Sorbo F" first="Francesca" last="Del Sorbo">Francesca Del Sorbo</name><name sortKey="Deuschl, Gunther" sort="Deuschl, Gunther" uniqKey="Deuschl G" first="Günther" last="Deuschl">Günther Deuschl</name><name sortKey="Edwards, Mark J" sort="Edwards, Mark J" uniqKey="Edwards M" first="Mark J" last="Edwards">Mark J. Edwards</name><name sortKey="G Mez Garre, Pilar" sort="G Mez Garre, Pilar" uniqKey="G Mez Garre P" first="Pilar" last="G Mez-Garre">Pilar G Mez-Garre</name><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><name sortKey="Graf, Julia" sort="Graf, Julia" uniqKey="Graf J" first="Julia" last="Graf">Julia Graf</name><name sortKey="Groen, Justus L" sort="Groen, Justus L" uniqKey="Groen J" first="Justus L" last="Groen">Justus L. Groen</name><name sortKey="Grunewald, Anne" sort="Grunewald, Anne" uniqKey="Grunewald A" first="Anne" last="Grünewald">Anne Grünewald</name><name sortKey="Hagenah, Johann" sort="Hagenah, Johann" uniqKey="Hagenah J" first="Johann" last="Hagenah">Johann Hagenah</name><name sortKey="Hemmelmann, Claudia" sort="Hemmelmann, Claudia" uniqKey="Hemmelmann C" first="Claudia" last="Hemmelmann">Claudia Hemmelmann</name><name sortKey="Jabusch, Hans Christian" sort="Jabusch, Hans Christian" uniqKey="Jabusch H" first="Hans-Christian" last="Jabusch">Hans-Christian Jabusch</name><name sortKey="Kaji, Ryuji" sort="Kaji, Ryuji" uniqKey="Kaji R" first="Ryuji" last="Kaji">Ryuji Kaji</name><name sortKey="Kasten, Meike" sort="Kasten, Meike" uniqKey="Kasten M" first="Meike" last="Kasten">Meike Kasten</name><name sortKey="Kawakami, Hideshi" sort="Kawakami, Hideshi" uniqKey="Kawakami H" first="Hideshi" last="Kawakami">Hideshi Kawakami</name><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><name sortKey="Kostic, Vladimir S" sort="Kostic, Vladimir S" uniqKey="Kostic V" first="Vladimir S" last="Kostic">Vladimir S. Kostic</name><name sortKey="Liguori, Maria" sort="Liguori, Maria" uniqKey="Liguori M" first="Maria" last="Liguori">Maria Liguori</name><name sortKey="Mir, Pablo" sort="Mir, Pablo" uniqKey="Mir P" first="Pablo" last="Mir">Pablo Mir</name><name sortKey="Munchau, Alexander" sort="Munchau, Alexander" uniqKey="Munchau A" first="Alexander" last="Münchau">Alexander Münchau</name><name sortKey="Ricchiuti, Felicia" sort="Ricchiuti, Felicia" uniqKey="Ricchiuti F" first="Felicia" last="Ricchiuti">Felicia Ricchiuti</name><name sortKey="Schillert, Arne" sort="Schillert, Arne" uniqKey="Schillert A" first="Arne" last="Schillert">Arne Schillert</name><name sortKey="Schmidt, Alexander" sort="Schmidt, Alexander" uniqKey="Schmidt A" first="Alexander" last="Schmidt">Alexander Schmidt</name><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name><name sortKey="Siegesmund, Katharina" sort="Siegesmund, Katharina" uniqKey="Siegesmund K" first="Katharina" last="Siegesmund">Katharina Siegesmund</name><name sortKey="Svetel, Marina" sort="Svetel, Marina" uniqKey="Svetel M" first="Marina" last="Svetel">Marina Svetel</name><name sortKey="Tijssen, Marina A J" sort="Tijssen, Marina A J" uniqKey="Tijssen M" first="Marina A J" last="Tijssen">Marina A J. Tijssen</name><name sortKey="Valente, Enza Maria" sort="Valente, Enza Maria" uniqKey="Valente E" first="Enza Maria" last="Valente">Enza Maria Valente</name><name sortKey="Westenberger, Ana" sort="Westenberger, Ana" uniqKey="Westenberger A" first="Ana" last="Westenberger">Ana Westenberger</name><name sortKey="Winkler, Susen" sort="Winkler, Susen" uniqKey="Winkler S" first="Susen" last="Winkler">Susen Winkler</name><name sortKey="Zeuner, Kirsten E" sort="Zeuner, Kirsten E" uniqKey="Zeuner K" first="Kirsten E" last="Zeuner">Kirsten E. Zeuner</name><name sortKey="Ziegler, Andreas" sort="Ziegler, Andreas" uniqKey="Ziegler A" first="Andreas" last="Ziegler">Andreas Ziegler</name><name sortKey="Zittel, Simone" sort="Zittel, Simone" uniqKey="Zittel S" first="Simone" last="Zittel">Simone Zittel</name></noCountry><country name="Allemagne"><noRegion><name sortKey="Lohmann, Katja" sort="Lohmann, Katja" uniqKey="Lohmann K" first="Katja" last="Lohmann">Katja Lohmann</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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