Abstract
We identified a marker in LINGO1 showing genome-wide significant association (P = 1.2 × 10−9, odds ratio = 1.55) with essential tremor. LINGO1 has potent, negative regulatory influences on neuronal survival and is also important in regulating both central-nervous-system axon regeneration and oligodendrocyte maturation. Increased axon integrity observed in Lingo1 mouse knockout models highlights the potential role of LINGO1 in the pathophysiology of essential tremor.
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Change history
24 March 2009
NOTE: In the version of this article initially published, one sentence in the abstract and two sentences in the final paragraph of the paper were in error and have been modified. The final sentence in the abstract should read: Increased axon integrity observed in Lingo1 mouse knockout models highlights the potential role of LINGO1 in the pathophysiology of ET. The final three sentences of the paper should read: Axonal swellings of Purkinje cell are considered to be one of the pathological findings in essential tremor6. Increased axon integrity observed in LINGO1 mouse knockout models16 highlights the potential role of LINGO1 in the pathophysiology of ET and opens up a new field in the research into essential tremor. It is our hope that LINGO1 will point the way to new treatments for severe cases of the disease. Finally, one reference has been added: 16. Mi, S. et al. Nat. Med. 13, 1228–1233 (2007). These errors have been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank the individuals taking part in this study whose contribution made this work possible. We also thank the Nurses at Krókháls (deCODE's recruitment center) and the personnel at the deCODE core facilities. The US sample was recruited through support from Emory General Clinical Research Center NIH/NCRR M01 RR00039 (CRIN Infra-structure support).
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The study was designed and results were interpreted by H.S., K.S., A.K., S.S., T.J., H.P., D.H. and J.G. Subject ascertainment and recruitment was carried out by K.S., J.B., J.G., F.J., K.K., M.D., L.S., F.A., A.R.R., L.A.M., C.M.T., C.H., E.A., A.Z., D.R., G.B., D.H. and G.A.J. Genotyping and laboratory experiments were performed by T.T., J.S., S.T.P., G.A.J., O.G., U.T., Y.B. and I.H.G. Authors H.S., K.S., S.S., O.G. and Y.B. drafted the manuscript. All authors contributed to the final version of the paper.
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Some of the authors, including Kari Stefansson (CEO of deCODE genetics), Jeffrey Gulcher (Chief Scientific Officer) and Augustine Kong (VP Statistics), are shareholders in deCODE genetics.
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Supplementary Methods, Supplementary Tables 1–4 and Supplementary Figures 1–3 (PDF 622 kb)
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Stefansson, H., Steinberg, S., Petursson, H. et al. Variant in the sequence of the LINGO1 gene confers risk of essential tremor. Nat Genet 41, 277–279 (2009). https://doi.org/10.1038/ng.299
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DOI: https://doi.org/10.1038/ng.299
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