Lack of association of LINGO1 rs9652490 and rs11856808 SNPs with familial essential tremor
Background: Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome‐wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET. Methods: We intended to replicate these findings by genotyping rs9652490 a...
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| Published in | European journal of neurology Vol. 18; no. 8; pp. 1085 - 1089 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.08.2011
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1351-5101 1468-1331 1468-1331 |
| DOI | 10.1111/j.1468-1331.2010.03251.x |
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| Abstract | Background: Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome‐wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET.
Methods: We intended to replicate these findings by genotyping rs9652490 and rs11856808 in a series of 226 familial ET subjects and 1117 healthy controls from referral movement disorder clinics in Spain.
Results: We were unable to replicate the association between LINGO1 variants and familial ET.
Conclusions: Our results indicate that the LINGO1 variants analyzed are not a major risk factor for developing familial ET in our population, which suggests the existence of other unknown genetic risk factors responsible for familial ET in the Spanish population. |
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| AbstractList | Background: Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome-wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET. Methods: We intended to replicate these findings by genotyping rs9652490 and rs11856808 in a series of 226 familial ET subjects and 1117 healthy controls from referral movement disorder clinics in Spain. Results: We were unable to replicate the association between LINGO1 variants and familial ET. Conclusions: Our results indicate that the LINGO1 variants analyzed are not a major risk factor for developing familial ET in our population, which suggests the existence of other unknown genetic risk factors responsible for familial ET in the Spanish population. Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome-wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET. We intended to replicate these findings by genotyping rs9652490 and rs11856808 in a series of 226 familial ET subjects and 1117 healthy controls from referral movement disorder clinics in Spain. We were unable to replicate the association between LINGO1 variants and familial ET. Our results indicate that the LINGO1 variants analyzed are not a major risk factor for developing familial ET in our population, which suggests the existence of other unknown genetic risk factors responsible for familial ET in the Spanish population. Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome-wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET.BACKGROUND Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome-wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET. We intended to replicate these findings by genotyping rs9652490 and rs11856808 in a series of 226 familial ET subjects and 1117 healthy controls from referral movement disorder clinics in Spain.METHODS We intended to replicate these findings by genotyping rs9652490 and rs11856808 in a series of 226 familial ET subjects and 1117 healthy controls from referral movement disorder clinics in Spain. We were unable to replicate the association between LINGO1 variants and familial ET.RESULTS We were unable to replicate the association between LINGO1 variants and familial ET. Our results indicate that the LINGO1 variants analyzed are not a major risk factor for developing familial ET in our population, which suggests the existence of other unknown genetic risk factors responsible for familial ET in the Spanish population.CONCLUSIONS Our results indicate that the LINGO1 variants analyzed are not a major risk factor for developing familial ET in our population, which suggests the existence of other unknown genetic risk factors responsible for familial ET in the Spanish population. Background: Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome‐wide association study has recently shown that LINGO1 gene variants are associated with increased risk of ET. Methods: We intended to replicate these findings by genotyping rs9652490 and rs11856808 in a series of 226 familial ET subjects and 1117 healthy controls from referral movement disorder clinics in Spain. Results: We were unable to replicate the association between LINGO1 variants and familial ET. Conclusions: Our results indicate that the LINGO1 variants analyzed are not a major risk factor for developing familial ET in our population, which suggests the existence of other unknown genetic risk factors responsible for familial ET in the Spanish population. |
| Author | Coria, F. Lorenzo, E. Alonso-Navarro, H. Jiménez-Jiménez, F. J. Luengo, A. Pastor, P. Lorenzo-Betancor, O. Cervantes, S. Irigoyen, J. García-Martín, E. Agúndez, J. A. G. |
| Author_xml | – sequence: 1 givenname: O. surname: Lorenzo-Betancor fullname: Lorenzo-Betancor, O. organization: Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona – sequence: 2 givenname: E. surname: García-Martín fullname: García-Martín, E. organization: Biochemistry and Molecular Biology, School of Biological Sciences, University of Extremadura, Badajoz – sequence: 3 givenname: S. surname: Cervantes fullname: Cervantes, S. organization: Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona – sequence: 4 givenname: J. A. G. surname: Agúndez fullname: Agúndez, J. A. G. organization: RIRAAF/RETICS, Redes Temáticas de Investigación Cooperativa en Salud, Instituto de Salud Carlos III, Spain – sequence: 5 givenname: F. J. surname: Jiménez-Jiménez fullname: Jiménez-Jiménez, F. J. organization: Department of Medicine-Neurology, Hospital ''Príncipe de Asturias'', Universidad de Alcalá, Madrid – sequence: 6 givenname: H. surname: Alonso-Navarro fullname: Alonso-Navarro, H. organization: Department of Neurology, Hospital del Sureste, Arganda del Rey, Madrid – sequence: 7 givenname: A. surname: Luengo fullname: Luengo, A. organization: Service of Neurology, Hospital La Princesa, University Hospital, Madrid – sequence: 8 givenname: F. surname: Coria fullname: Coria, F. organization: Clinic for Nervous System Disorders and Service of Neurology, Hospital Universitario Son Dureta, Palma de Mallorca – sequence: 9 givenname: E. surname: Lorenzo fullname: Lorenzo, E. organization: Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona – sequence: 10 givenname: J. surname: Irigoyen fullname: Irigoyen, J. organization: Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona – sequence: 11 givenname: P. surname: Pastor fullname: Pastor, P. organization: Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona |
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| References | Martinez C, Garcia-Martin E, Alonso-Navarro H, et al. Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor. Neuromolecular Med 2007; 9: 195-204. Higgins JJ, Pho LT, Nee LE. A gene (ETM) for essential tremor maps to chromosome 2p22-p25. Mov Disord 1997; 12: 859-864. Inoue H, Lin L, Lee X, et al. Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models. Proc Natl Acad Sci USA 2007; 104: 14430-14435. Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559-575. Stefansson H, Steinberg S, Petursson H, et al. Variant in the sequence of the LINGO1 gene confers risk of essential tremor. Nat Genet 2009; 41: 277-279. Louis ED. Etiology of essential tremor: should we be searching for environmental causes? Mov Disord 2001; 16: 822-829. Thier S, Lorenz D, Nothnagel M, et al. LINGO1 polymorphisms are associated with essential tremor in Europeans. Mov Disord 2010; 25: 709-715. Lorenzo-Betancor O, Samaranch L, García-Martín E, et al. LINGO1 gene analysis in Parkinson's disease phenotypes. Mov Disord 2010; n/a. doi: 10.1002/mds. 23452. Shatunov A, Sambuughin N, Jankovic J, et al. Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23. Brain 2006; 129: 2318-2331. Jeanneteau F, Funalot B, Jankovic J, et al. A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Proc Natl Acad Sci USA 2006; 103: 10753-10758. Paisan-Ruiz C, Jain S, Evans EW, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 2004; 44: 595-600. Pastor P, Roe CM, Villegas A, et al. Apolipoprotein Eepsilon4 modifies Alzheimer's disease onset in an E280A PS1 kindred. Ann Neurol 2003; 54: 163-169. Zimprich A, Biskup S, Leitner P, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 2004; 44: 601-607. Mi S, Lee X, Shao Z, et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci 2004; 7: 221-228. Vilarino-Guell C, Wider C, Ross OA, et al. LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease. Neurogenetics 2010; 11: 401-408. Gulcher JR, Jonsson P, Kong A, et al. Mapping of a familial essential tremor gene, FET1, to chromosome 3q13. Nat Genet 1997; 17: 84-87. Clark LN, Park N, Kisselev S, Rios E, Lee JH, Louis ED. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet 2010; 18: 838-843. Tan EK, Teo YY, Prakash KM, et al. LINGO1 variant increases risk of familial essential tremor. Neurology 2009; 73: 1161-1162. Vilariño-Güell C, Ross OA, Wider C, et al. LINGO1 rs9652490 is associated with essential tremor and Parkinson disease. Parkinsonism Relat Disord 2010; 16: 109-111. Cruchaga C, Vidal-Taboada JM, Ezquerra M, et al. 5′-Upstream variants of CRHR1 and MAPT genes associated with age at onset in progressive supranuclear palsy and cortical basal degeneration. Neurobiol Dis 2009; 33: 164-170. Jankovic J. Essential tremor: a heterogenous disorder. Mov Disord 2002; 17: 638-644. Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord 1998; 13(Suppl. 3): 2-23. Martinez C, Garcia-Martin E, Alonso-Navarro H, et al. Glutathione-S-transferase P1 polymorphism and risk for essential tremor. Eur J Neurol 2008; 15: 234-238. Magi R, Morris AP. GWAMA: software for genome-wide association meta-analysis. BMC Bioinformatics 2010; 11: 288. Garcia-Martin E, Martinez C, Alonso-Navarro H, et al. Dopamine receptor D3 (DRD3) genotype and allelic variants and risk for essential tremor. Mov Disord 2009; 24: 1910-1915. Dudbridge F. Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 2003; 25: 115-121. Alonso-Navarro H, Martinez C, Garcia-Martin E, et al. CYP2C19 polymorphism and risk for essential tremor. Eur Neurol 2006; 56: 119-123. 2002; 17 2007; 104 2004; 44 2010; 11 2009; 24 2009; 41 2010; 16 2006; 56 2010 2010; 18 2004; 7 2008; 15 2006 2003; 54 2009; 33 2009; 73 2010; 25 1997; 12 2007; 9 2003; 25 1997; 17 2007; 81 2001; 16 2006; 129 2006; 103 1998; 13 |
| References_xml | – reference: Higgins JJ, Pho LT, Nee LE. A gene (ETM) for essential tremor maps to chromosome 2p22-p25. Mov Disord 1997; 12: 859-864. – reference: Alonso-Navarro H, Martinez C, Garcia-Martin E, et al. CYP2C19 polymorphism and risk for essential tremor. Eur Neurol 2006; 56: 119-123. – reference: Dudbridge F. Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 2003; 25: 115-121. – reference: Louis ED. Etiology of essential tremor: should we be searching for environmental causes? Mov Disord 2001; 16: 822-829. – reference: Stefansson H, Steinberg S, Petursson H, et al. Variant in the sequence of the LINGO1 gene confers risk of essential tremor. Nat Genet 2009; 41: 277-279. – reference: Garcia-Martin E, Martinez C, Alonso-Navarro H, et al. Dopamine receptor D3 (DRD3) genotype and allelic variants and risk for essential tremor. Mov Disord 2009; 24: 1910-1915. – reference: Thier S, Lorenz D, Nothnagel M, et al. LINGO1 polymorphisms are associated with essential tremor in Europeans. Mov Disord 2010; 25: 709-715. – reference: Jeanneteau F, Funalot B, Jankovic J, et al. A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Proc Natl Acad Sci USA 2006; 103: 10753-10758. – reference: Zimprich A, Biskup S, Leitner P, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 2004; 44: 601-607. – reference: Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord 1998; 13(Suppl. 3): 2-23. – reference: Martinez C, Garcia-Martin E, Alonso-Navarro H, et al. Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor. Neuromolecular Med 2007; 9: 195-204. – reference: Mi S, Lee X, Shao Z, et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci 2004; 7: 221-228. – reference: Lorenzo-Betancor O, Samaranch L, García-Martín E, et al. LINGO1 gene analysis in Parkinson's disease phenotypes. Mov Disord 2010; n/a. doi: 10.1002/mds. 23452. – reference: Magi R, Morris AP. GWAMA: software for genome-wide association meta-analysis. BMC Bioinformatics 2010; 11: 288. – reference: Shatunov A, Sambuughin N, Jankovic J, et al. Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23. Brain 2006; 129: 2318-2331. – reference: Vilarino-Guell C, Wider C, Ross OA, et al. LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease. Neurogenetics 2010; 11: 401-408. – reference: Jankovic J. Essential tremor: a heterogenous disorder. Mov Disord 2002; 17: 638-644. – reference: Gulcher JR, Jonsson P, Kong A, et al. Mapping of a familial essential tremor gene, FET1, to chromosome 3q13. Nat Genet 1997; 17: 84-87. – reference: Cruchaga C, Vidal-Taboada JM, Ezquerra M, et al. 5′-Upstream variants of CRHR1 and MAPT genes associated with age at onset in progressive supranuclear palsy and cortical basal degeneration. Neurobiol Dis 2009; 33: 164-170. – reference: Paisan-Ruiz C, Jain S, Evans EW, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 2004; 44: 595-600. – reference: Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559-575. – reference: Inoue H, Lin L, Lee X, et al. Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models. Proc Natl Acad Sci USA 2007; 104: 14430-14435. – reference: Pastor P, Roe CM, Villegas A, et al. Apolipoprotein Eepsilon4 modifies Alzheimer's disease onset in an E280A PS1 kindred. Ann Neurol 2003; 54: 163-169. – reference: Vilariño-Güell C, Ross OA, Wider C, et al. LINGO1 rs9652490 is associated with essential tremor and Parkinson disease. Parkinsonism Relat Disord 2010; 16: 109-111. – reference: Martinez C, Garcia-Martin E, Alonso-Navarro H, et al. Glutathione-S-transferase P1 polymorphism and risk for essential tremor. Eur J Neurol 2008; 15: 234-238. – reference: Clark LN, Park N, Kisselev S, Rios E, Lee JH, Louis ED. Replication of the LINGO1 gene association with essential tremor in a North American population. Eur J Hum Genet 2010; 18: 838-843. – reference: Tan EK, Teo YY, Prakash KM, et al. LINGO1 variant increases risk of familial essential tremor. Neurology 2009; 73: 1161-1162. – volume: 15 start-page: 234 year: 2008 end-page: 238 article-title: Glutathione‐S‐transferase P1 polymorphism and risk for essential tremor publication-title: Eur J Neurol – volume: 25 start-page: 115 year: 2003 end-page: 121 article-title: Pedigree disequilibrium tests for multilocus haplotypes publication-title: Genet Epidemiol – volume: 25 start-page: 709 year: 2010 end-page: 715 article-title: LINGO1 polymorphisms are associated with essential tremor in Europeans publication-title: Mov Disord – year: 2010 article-title: LINGO1 gene analysis in Parkinson’s disease phenotypes publication-title: Mov Disord – volume: 13 start-page: 2 issue: Suppl. 3 year: 1998 end-page: 23 article-title: Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee publication-title: Mov Disord – volume: 11 start-page: 288 year: 2010 article-title: GWAMA: software for genome‐wide association meta‐analysis publication-title: BMC Bioinformatics – volume: 41 start-page: 277 year: 2009 end-page: 279 article-title: Variant in the sequence of the LINGO1 gene confers risk of essential tremor publication-title: Nat Genet – volume: 81 start-page: 559 year: 2007 end-page: 575 article-title: PLINK: a tool set for whole‐genome association and population‐based linkage analyses publication-title: Am J Hum Genet – volume: 103 start-page: 10753 year: 2006 end-page: 10758 article-title: A functional variant of the dopamine D3 receptor is associated with risk and age‐at‐onset of essential tremor publication-title: Proc Natl Acad Sci USA – volume: 24 start-page: 1910 year: 2009 end-page: 1915 article-title: Dopamine receptor D3 (DRD3) genotype and allelic variants and risk for essential tremor publication-title: Mov Disord – volume: 129 start-page: 2318 year: 2006 end-page: 2331 article-title: Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23 publication-title: Brain – volume: 73 start-page: 1161 year: 2009 end-page: 1162 article-title: LINGO1 variant increases risk of familial essential tremor publication-title: Neurology – volume: 44 start-page: 595 year: 2004 end-page: 600 article-title: Cloning of the gene containing mutations that cause PARK8‐linked Parkinson’s disease publication-title: Neuron – volume: 17 start-page: 84 year: 1997 end-page: 87 article-title: Mapping of a familial essential tremor gene, FET1, to chromosome 3q13 publication-title: Nat Genet – volume: 12 start-page: 859 year: 1997 end-page: 864 article-title: A gene (ETM) for essential tremor maps to chromosome 2p22‐p25 publication-title: Mov Disord – volume: 17 start-page: 638 year: 2002 end-page: 644 article-title: Essential tremor: a heterogenous disorder publication-title: Mov Disord – volume: 16 start-page: 822 year: 2001 end-page: 829 article-title: Etiology of essential tremor: should we be searching for environmental causes? publication-title: Mov Disord – year: 2006 – volume: 56 start-page: 119 year: 2006 end-page: 123 article-title: CYP2C19 polymorphism and risk for essential tremor publication-title: Eur Neurol – volume: 16 start-page: 109 year: 2010 end-page: 111 article-title: LINGO1 rs9652490 is associated with essential tremor and Parkinson disease publication-title: Parkinsonism Relat Disord – volume: 7 start-page: 221 year: 2004 end-page: 228 article-title: LINGO‐1 is a component of the Nogo‐66 receptor/p75 signaling complex publication-title: Nat Neurosci – volume: 44 start-page: 601 year: 2004 end-page: 607 article-title: Mutations in LRRK2 cause autosomal‐dominant parkinsonism with pleomorphic pathology publication-title: Neuron – volume: 9 start-page: 195 year: 2007 end-page: 204 article-title: Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor publication-title: Neuromolecular Med – volume: 104 start-page: 14430 year: 2007 end-page: 14435 article-title: Inhibition of the leucine‐rich repeat protein LINGO‐1 enhances survival, structure, and function of dopaminergic neurons in Parkinson’s disease models publication-title: Proc Natl Acad Sci USA – volume: 18 start-page: 838 year: 2010 end-page: 843 article-title: Replication of the LINGO1 gene association with essential tremor in a North American population publication-title: Eur J Hum Genet – volume: 33 start-page: 164 year: 2009 end-page: 170 article-title: 5′‐Upstream variants of CRHR1 and MAPT genes associated with age at onset in progressive supranuclear palsy and cortical basal degeneration publication-title: Neurobiol Dis – volume: 54 start-page: 163 year: 2003 end-page: 169 article-title: Apolipoprotein Eepsilon4 modifies Alzheimer’s disease onset in an E280A PS1 kindred publication-title: Ann Neurol – volume: 11 start-page: 401 year: 2010 end-page: 408 article-title: LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease publication-title: Neurogenetics |
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| Snippet | Background: Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome‐wide association study has recently shown... Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome-wide association study has recently shown that LINGO1... Background: Essential tremor (ET) is a frequent movement disorder with a substantial family aggregation. A genome-wide association study has recently shown... |
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| SubjectTerms | Adolescent Adult Aged Aged, 80 and over association study Case-Control Studies essential tremor Essential Tremor - epidemiology Essential Tremor - genetics Gene Frequency - genetics Genetic Predisposition to Disease - genetics Genetic Testing genetics Genotype Genotyping Humans LINGO1 Membrane Proteins - genetics Middle Aged Movement disorders Nerve Tissue Proteins - genetics Polymorphism, Single Nucleotide - genetics Risk Factors Single-nucleotide polymorphism tremor Young Adult |
| Title | Lack of association of LINGO1 rs9652490 and rs11856808 SNPs with familial essential tremor |
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