Sandra Thier

Publications (6)29.1 Total impact

• Article: No Association Between Polymorphisms in the Glutamate Transporter SLC1A2 and Parkinson's Disease.

  Silke Appenzeller, Claudia Schulte, Sandra Thier, Franziska Hopfner, Manuela Pendziwiat, Frank Papengut, Christine Klein, Johann Hagenah, Meike Kasten, Karin Srulijes, Daniela Berg, Thomas Gasser, Andrew Singleton, Günther Deuschl, Gregor Kuhlenbäumer
  Movement Disorders 02/2013; · 4.51 Impact Factor
• Article: No association between NOD2 variants and Parkinson's disease.

  Silke Appenzeller, Sandra Thier, Frank Papengut, Christine Klein, Johann Hagenah, Meike Kasten, Daniela Berg, Karin Srulijes, Thomas Gasser, Stefan Schreiber, Günther Deuschl, Gregor Kuhlenbäumer
  Movement Disorders 07/2012; 27(9):1191-2. · 4.51 Impact Factor
• Article: Polymorphisms in the glial glutamate transporter SLC1A2 are associated with essential tremor.

  Sandra Thier, Delia Lorenz, Michael Nothnagel, Caroline Poremba, Frank Papengut, Silke Appenzeller, Steffen Paschen, Frank Hofschulte, Anna-Christina Hussl, Sascha Hering, Werner Poewe, Friedrich Asmus, Thomas Gasser, Ludger Schöls, Kaare Christensen, Almut Nebel, Stefan Schreiber, Stephan Klebe, Günther Deuschl, Gregor Kuhlenbäumer
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  ABSTRACT: Sporadic, genetically complex essential tremor (ET) is one of the most common movement disorders and may lead to severe impairment of the quality of life. Despite high heritability, the genetic determinants of ET are largely unknown. We performed the second genome-wide association study (GWAS) for ET to elucidate genetic risk factors of ET. Using the Affymetrix Genome-Wide SNP Array 6.0 (1000K) we conducted a two-stage GWAS in a total of 990 subjects and 1,537 control subjects from Europe to identify genetic variants associated with ET. We discovered association of an intronic variant of the main glial glutamate transporter (SLC1A2) gene with ET in the first-stage sample (rs3794087, p = 6.95 × 10(-5), odds ratio [OR] = 1.46). We verified the association of rs3794087 with ET in a second-stage sample (p = 1.25 × 10(-3), OR = 1.38). In the subgroup analysis of patients classified as definite ET, rs3794087 obtained genome-wide significance (p = 3.44 × 10(-10), OR = 1.59) in the combined first- and second-stage sample. Genetic fine mapping using nonsynonymous single nucleotide polymorphisms (SNPs) and SNPs in high linkage disequilibrium with rs3794087 did not reveal any SNP with a stronger association with ET than rs3794087. We identified SLC1A2 encoding the major glial high-affinity glutamate reuptake transporter in the brain as a potential ET susceptibility gene. Acute and chronic glutamatergic overexcitation is implied in the pathogenesis of ET. SLC1A2 is therefore a good functional candidate gene for ET.
  Neurology 07/2012; 79(3):243-8. · 8.31 Impact Factor
• Article: LINGO1 is not associated with Parkinson's disease in German patients.

  Stephan Klebe, Sandra Thier, Delia Lorenz, Michael Nothnagel, Stefan Schreiber, Christine Klein, Johann Hagenah, Meike Kasten, Daniela Berg, Karin Srulijes, Thomas Gasser, Günther Deuschl, Gregor Kuhlenbäumer
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  ABSTRACT: Essential tremor (ET) and Parkinson's disease (PD) are the most common movement disorders and show clinical, genetic, and pathophysiological overlap. Single-nucleotide polymorphisms (SNPs) in the leucine-rich repeat (LRR) and immunoglobulin (Ig) domain-containing, Nogo receptor-interacting protein gene (LINGO1) are associated with ET. LINGO1 is overexpressed in the substantia nigra (SN) of PD patients and inhibition of LINGO1 confers neuroprotection in a rodent model of PD. In this study we test the hypothesis whether SNPs in the LINGO1 gene that are associated with ET are also associated with PD. Three large German case-control samples from Kiel, Lübeck, and Tübingen (total: 1,798 cases and 1,482 controls) were genotyped for the three LINGO1 SNPs associated with ET. Association was assessed using allele- and genotype-based tests in each of the three samples separately, in the combined sample, and in subsets of patients with early-onset PD (<50 years) and of patients with a positive family history of PD. Neither of the three samples alone nor the combined sample showed evidence for association between LINGO1 SNPs and PD. The allele-based test showed a trend toward nominal association for all three SNPs in the Kiel sample. The subsets with early-onset PD or a positive family history did also not reveal evidence for association. SNPs in the LINGO1 gene associated with ET could not be shown to be associated with PD in our study population, despite a postulated overlap between both diseases.
  American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2010; 153B(6):1173-8. · 3.70 Impact Factor
• Article: LINGO1 polymorphisms are associated with essential tremor in Europeans.

  Sandra Thier, Delia Lorenz, Michael Nothnagel, Giovanni Stevanin, Alexandra Dürr, Almut Nebel, Stefan Schreiber, Gregor Kuhlenbäumer, Günther Deuschl, Stephan Klebe
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  ABSTRACT: Essential tremor (ET) is one of the most common movement disorders. Former association studies focussing on candidate genes in ET found a number of risk variants but most of them were not replicated. Recently, a genome-wide association study revealed two intronic sequence variants in the LINGO1 gene associated with ET. Here, we have confirmed association between sequence variants in the LINGO1 gene and the ET phenotype in independent German and French ET samples. The odds ratios for the identified intronic markers rs8030859 (P = 1.0x10(-4)), rs9652490 (P = 9.1x10(-4)), and rs11856808 (P = 3.6x10(-2)) were 1.72 (CI 1.31-2.26), 1.61 (CI 1.21-2.14), and 1.30 (CI 1.02-1.66), respectively, in our German sample. LINGO1 is an interesting candidate gene because it plays a key role in central nervous system biology, is selectively expressed in the nervous system, and is an inhibitor of oligodendrocyte differentiation and neuronal myelination. Our study gives further evidence that LINGO1 acts as a susceptibility gene for ET.
  Movement Disorders 03/2010; 25(6):717-23. · 4.51 Impact Factor
• Article: Dopamine receptor D3 gene and essential tremor in large series of German, Danish and French patients.

  Delia Lorenz, Stephan Klebe, Giovanni Stevanin, Sandra Thier, Almut Nebel, Josué Feingold, Henrik Frederiksen, Elodie Denis, Kaare Christensen, Stefan Schreiber, Alexis Brice, Günther Deuschl, Alexandra Dürr
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  ABSTRACT: The genetic causes of essential tremor (ET) seem to be heterogeneous. Recently, ET has been found associated with a functional variant (Ser9Gly) of the dopamine D(3) receptor (DRD3), located in the ETM1 locus on chromosome 3q13.3 described for the first time in 1997. We examined this variant in three different populations from Germany, Denmark and France. We undertook an association study of the Ser9Gly variant in 202 cases with a familial history from unrelated families with ET, 97 cases with isolated non-familial ET and 528 healthy controls. In addition, linkage and segregation analyses were carried out in 22 ET families. The distribution of genotypes and allele frequencies showed no significant differences in the whole sample and in a subanalysis of familial and sporadic cases. Age at onset of tremor, tremor duration and tremor severity did not show an association with the genotype. In addition, the DRD3 variant was not found linked to the disease in a subset of informative ET families. We did not find a significant association of the DRD3 variant with ET nor linkage to the DRD3 receptor in German, Danish and French ET patients and families, suggesting that it is unlikely to be a causal factor for ET.
  European journal of human genetics: EJHG 01/2009; 17(6):766-73. · 3.56 Impact Factor