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LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease

Content Provider	Springer Nature Link
Author	Vilariño Güell, Carles Wider, Christian Ross, Owen A. Jasinska Myga, Barbara Kachergus, Jennifer Cobb, Stephanie A. Soto Ortolaza, Alexandra I. Behrouz, Bahareh Heckman, Michael G. Diehl, Nancy N. Testa, Claudia M. Wszolek, Zbigniew K. Uitti, Ryan J. Jankovic, Joseph Louis, Elan D. Clark, Lorraine N. Rajput, Alex Farrer, Matthew J.
Copyright Year	2010
Abstract	Genetic variation in the leucine-rich repeat and Ig domain containing 1 gene (LINGO1) was recently associated with an increased risk of developing essential tremor (ET) and Parkinson disease (PD). Herein, we performed a comprehensive study of LINGO1 and its paralog LINGO2 in ET and PD by sequencing both genes in patients (ET, n = 95; PD, n = 96) and by examining haplotype-tagging single-nucleotide polymorphisms (tSNPs) in a multicenter North American series of patients (ET, n = 1,247; PD, n = 633) and controls (n = 642). The sequencing study identified six novel coding variants in LINGO1 (p.S4C, p.V107M, p.A277T, p.R423R, p.G537A, p.D610D) and three in LINGO2 (p.D135D, p.P217P, p.V565V), however segregation analysis did not support pathogenicity. The association study employed 16 tSNPs at the LINGO1 locus and 21 at the LINGO2 locus. One variant in LINGO1 (rs9652490) displayed evidence of an association with ET (odds ratio (OR) = 0.63; P = 0.026) and PD (OR = 0.54; P = 0.016). Additionally, four other tSNPs in LINGO1 and one in LINGO2 were associated with ET and one tSNP in LINGO2 associated with PD (P < 0.05). Further analysis identified one tSNP in LINGO1 and two in LINGO2 which influenced age at onset of ET and two tSNPs in LINGO1 which altered age at onset of PD (P < 0.05). Our results support a role for LINGO1 and LINGO2 in determining risk for and perhaps age at onset of ET and PD. Further studies are warranted to confirm these findings and to determine the pathogenic mechanisms involved.
Starting Page	401
Ending Page	408
Page Count	8
File Format	PDF
ISSN	13646745
Journal	Neurogenetics
Volume Number	11
Issue Number	4
e-ISSN	13646753
Language	English
Publisher	Springer-Verlag
Publisher Date	2010-04-06
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Essential tremor Parkinson disease LINGO1 LINGO2 Genetic association Neurosciences Molecular Medicine Human Genetics
Content Type	Text
Resource Type	Article
Subject	Genetics Cellular and Molecular Neuroscience Genetics (clinical)

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