title: LINGO1 is not associated with Parkinson's disease in German patients.
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.
authors.affiliation: Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller Strasse 3, Kiel, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Klebe
authors.forename: Sandra
authors.initials: S
authors.lastname: Thier
authors.forename: Delia
authors.initials: D
authors.lastname: Lorenz
authors.forename: Michael
authors.initials: M
authors.lastname: Nothnagel
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Johann
authors.initials: J
authors.lastname: Hagenah
authors.forename: Meike
authors.initials: M
authors.lastname: Kasten
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.forename: Karin
authors.initials: K
authors.lastname: Srulijes
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.forename: Günther
authors.initials: G
authors.lastname: Deuschl
authors.forename: Gregor
authors.initials: G
authors.lastname: Kuhlenbäumer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins