title: Genetics of essential tremor: meta-analysis and review.
abstract: OBJECTIVE
  To provide a comprehensive meta-analysis and review of the clinical and molecular genetics of essential tremor (ET).
  
  
  METHODS
  Studies were reviewed from the literature. Linkage studies were analyzed applying criteria used for monogenic disorders. For association studies, allele counts were extracted and allelic association calculated whenever possible. A meta-analysis was performed for genetic markers investigated in more than 3 studies.
  
  
  RESULTS
  Linkage studies have shown conclusive results in a single family only for the locus ETM2 (essential tremor monogenetic locus 2, logarithm of odds score [lod] > 3.3). None of the 3 ETM loci has been confirmed independently with a lod score >2.0 in a single family. A mutation in the FUS gene (fused in sarcoma) was found in one ET family by exome sequencing. Two genome-wide association studies demonstrated association between variants in the LINGO1 gene (leucine-rich repeat and Ig domain containing 1) and the SLC1A2 gene (solute carrier family 1 member 2) and ET, respectively. Our meta-analysis confirmed the association of rs9652490 in LINGO1 with ET. Candidate gene mutation analysis and association studies have not identified reproducible associations.
  
  
  CONCLUSIONS
  Problems of genetic studies of ET are caused by the lack of stringent diagnostic criteria, small sample sizes, lack of biomarkers, a high phenocopy rate, evidence for nonmendelian inheritance, and high locus heterogeneity in presumably monogenic ET. These issues could be resolved by better worldwide cooperation and the use of novel genetic techniques.
authors: From the Institute of Experimental Medicine (G.K., F.H.), Christian-Albrechts-University Kiel; and the Department of Neurology (F.H., G.D.), University Hospital Schleswig-Holstein, Campus Kiel, Germany. G.K. is currently with the Department of Neurology, University Hospital Schleswig-Holstein.
authors: Gregor
authors: G
authors: Kuhlenbäumer
authors: Franziska
authors: F
authors: Hopfner
authors: Günther
authors: G
authors: Deuschl
mesh_terms: D020329:Essential Tremor / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D039781:PubMed / Q000706:statistics & numerical data
chemical_list: D009419:Nerve Tissue Proteins