👤 Michael Nothnagel

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. Show less

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. Show less