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

Identifieur interne : 000256 ( Pmc/Curation ); précédent : 000255; suivant : 000257

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

Auteurs : Carles Vilari ; Christian Wider ; Owen Ross ; Barbara Jasinska ; Jennifer Kachergus ; Stephanie Cobb ; Alexandra Soto ; Bahareh Behrouz ; Michael Heckman ; Nancy Diehl ; Claudia Testa ; Zbigniew Wszolek ; Ryan Uitti ; Joseph Jankovic ; Elan Louis ; Lorraine Clark ; Alex Rajput ; Matthew Farrer

Source :

RBID : PMC:3930084

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.


Url:
DOI: 10.1007/s10048-010-0241-x
PubMed: 20369371
PubMed Central: 3930084

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PMC:3930084

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and
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variants are associated with essential tremor and Parkinson disease</title>
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<name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari">Carles Vilari</name>
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<italic>LINGO1</italic>
and
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variants are associated with essential tremor and Parkinson disease</title>
<author>
<name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari">Carles Vilari</name>
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<name sortKey="Wider, Christian" sort="Wider, Christian" uniqKey="Wider C" first="Christian" last="Wider">Christian Wider</name>
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<author>
<name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska">Barbara Jasinska</name>
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<name sortKey="Kachergus, Jennifer" sort="Kachergus, Jennifer" uniqKey="Kachergus J" first="Jennifer" last="Kachergus">Jennifer Kachergus</name>
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<name sortKey="Cobb, Stephanie A" sort="Cobb, Stephanie A" uniqKey="Cobb S" first="Stephanie" last="Cobb">Stephanie Cobb</name>
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<author>
<name sortKey="Soto Ortolaza, Alexandra I" sort="Soto Ortolaza, Alexandra I" uniqKey="Soto Ortolaza A" first="Alexandra" last="Soto">Alexandra Soto</name>
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<author>
<name sortKey="Behrouz, Bahareh" sort="Behrouz, Bahareh" uniqKey="Behrouz B" first="Bahareh" last="Behrouz">Bahareh Behrouz</name>
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<name sortKey="Testa, Claudia M" sort="Testa, Claudia M" uniqKey="Testa C" first="Claudia" last="Testa">Claudia Testa</name>
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<author>
<name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew" last="Wszolek">Zbigniew Wszolek</name>
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<author>
<name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan" last="Uitti">Ryan Uitti</name>
</author>
<author>
<name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
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<name sortKey="Louis, Elan D" sort="Louis, Elan D" uniqKey="Louis E" first="Elan" last="Louis">Elan Louis</name>
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<author>
<name sortKey="Clark, Lorraine N" sort="Clark, Lorraine N" uniqKey="Clark L" first="Lorraine" last="Clark">Lorraine Clark</name>
</author>
<author>
<name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name>
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<div type="abstract" xml:lang="en">
<p id="P1">Genetic variation in the leucine-rich repeat and Ig domain containing 1 gene (
<italic>LINGO1</italic>
) was recently associated with an increased risk of developing essential tremor (ET) and Parkinson disease (PD). Herein, we performed a comprehensive study of
<italic>LINGO1</italic>
and its paralog
<italic>LINGO2</italic>
in ET and PD by sequencing both genes in patients (ET,
<italic>n</italic>
=95; PD,
<italic>n</italic>
=96) and by examining haplotype-tagging single-nucleotide polymorphisms (tSNPs) in a multicenter North American series of patients (ET,
<italic>n</italic>
=1,247; PD,
<italic>n</italic>
=633) and controls (
<italic>n</italic>
=642). The sequencing study identified six novel coding variants in
<italic>LINGO1</italic>
(p.S4C, p.V107M, p.A277T, p.R423R, p.G537A, p.D610D) and three in
<italic>LINGO2</italic>
(p.D135D, p.P217P, p.V565V), however segregation analysis did not support pathogenicity. The association study employed 16 tSNPs at the
<italic>LINGO1</italic>
locus and 21 at the
<italic>LINGO2</italic>
locus. One variant in
<italic>LINGO1</italic>
(rs9652490) displayed evidence of an association with ET (odds ratio (OR)=0.63;
<italic>P</italic>
=0.026) and PD (OR=0.54;
<italic>P</italic>
=0.016). Additionally, four other tSNPs in
<italic>LINGO1</italic>
and one in
<italic>LINGO2</italic>
were associated with ET and one tSNP in
<italic>LINGO2</italic>
associated with PD (
<italic>P</italic>
<0.05). Further analysis identified one tSNP in
<italic>LINGO1</italic>
and two in
<italic>LINGO2</italic>
which influenced age at onset of ET and two tSNPs in
<italic>LINGO1</italic>
which altered age at onset of PD (
<italic>P</italic>
<0.05). Our results support a role for
<italic>LINGO1</italic>
and
<italic>LINGO2</italic>
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.</p>
</div>
</front>
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<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">9709714</journal-id>
<journal-id journal-id-type="pubmed-jr-id">20757</journal-id>
<journal-id journal-id-type="nlm-ta">Neurogenetics</journal-id>
<journal-id journal-id-type="iso-abbrev">Neurogenetics</journal-id>
<journal-title-group>
<journal-title>Neurogenetics</journal-title>
</journal-title-group>
<issn pub-type="ppub">1364-6745</issn>
<issn pub-type="epub">1364-6753</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">20369371</article-id>
<article-id pub-id-type="pmc">3930084</article-id>
<article-id pub-id-type="doi">10.1007/s10048-010-0241-x</article-id>
<article-id pub-id-type="manuscript">NIHMS549504</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>
<italic>LINGO1</italic>
and
<italic>LINGO2</italic>
variants are associated with essential tremor and Parkinson disease</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Vilariño-Güell</surname>
<given-names>Carles</given-names>
</name>
<aff id="A1">Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wider</surname>
<given-names>Christian</given-names>
</name>
<aff id="A2">Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Department of Neurology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ross</surname>
<given-names>Owen A.</given-names>
</name>
<aff id="A3">Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jasinska-Myga</surname>
<given-names>Barbara</given-names>
</name>
<aff id="A4">Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Department of Neurology, Medical University of Silesia, Katowice, Poland</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kachergus</surname>
<given-names>Jennifer</given-names>
</name>
<aff id="A5">Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cobb</surname>
<given-names>Stephanie A.</given-names>
</name>
<aff id="A6">Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Soto-Ortolaza</surname>
<given-names>Alexandra I.</given-names>
</name>
<aff id="A7">Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Behrouz</surname>
<given-names>Bahareh</given-names>
</name>
<aff id="A8">Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Heckman</surname>
<given-names>Michael G.</given-names>
</name>
<aff id="A9">Biostatistics Unit, Mayo Clinic, Jacksonville, FL, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Diehl</surname>
<given-names>Nancy N.</given-names>
</name>
<aff id="A10">Biostatistics Unit, Mayo Clinic, Jacksonville, FL, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Testa</surname>
<given-names>Claudia M.</given-names>
</name>
<aff id="A11">Emory Department of Neurology and Center for Neurodegenerative Diseases, Whitehead Biomedical Research Building, Atlanta, GA, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wszolek</surname>
<given-names>Zbigniew K.</given-names>
</name>
<aff id="A12">Department of Neurology, Mayo Clinic, Jacksonville, FL, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Uitti</surname>
<given-names>Ryan J.</given-names>
</name>
<aff id="A13">Department of Neurology, Mayo Clinic, Jacksonville, FL, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jankovic</surname>
<given-names>Joseph</given-names>
</name>
<aff id="A14">Department of Neurology, Parkinson’s Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, TX, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Louis</surname>
<given-names>Elan D.</given-names>
</name>
<aff id="A15">GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Clark</surname>
<given-names>Lorraine N.</given-names>
</name>
<aff id="A16">Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA</aff>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rajput</surname>
<given-names>Alex</given-names>
</name>
<aff id="A17">Division of Neurology, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada</aff>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Farrer</surname>
<given-names>Matthew J.</given-names>
</name>
<aff id="A18">Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA</aff>
<email>Farrer.Matthew@mayo.edu</email>
</contrib>
</contrib-group>
<author-notes>
<fn id="FN1" fn-type="equal">
<p>Carles Vilariño-Güell and Christian Wider have contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>7</day>
<month>2</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub">
<day>06</day>
<month>4</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="ppub">
<month>10</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>20</day>
<month>2</month>
<year>2014</year>
</pub-date>
<volume>11</volume>
<issue>4</issue>
<fpage>401</fpage>
<lpage>408</lpage>
<pmc-comment>elocation-id from pubmed: 10.1007/s10048-010-0241-x</pmc-comment>
<permissions>
<copyright-statement>© Springer-Verlag 2010</copyright-statement>
<copyright-year>2010</copyright-year>
</permissions>
<abstract>
<p id="P1">Genetic variation in the leucine-rich repeat and Ig domain containing 1 gene (
<italic>LINGO1</italic>
) was recently associated with an increased risk of developing essential tremor (ET) and Parkinson disease (PD). Herein, we performed a comprehensive study of
<italic>LINGO1</italic>
and its paralog
<italic>LINGO2</italic>
in ET and PD by sequencing both genes in patients (ET,
<italic>n</italic>
=95; PD,
<italic>n</italic>
=96) and by examining haplotype-tagging single-nucleotide polymorphisms (tSNPs) in a multicenter North American series of patients (ET,
<italic>n</italic>
=1,247; PD,
<italic>n</italic>
=633) and controls (
<italic>n</italic>
=642). The sequencing study identified six novel coding variants in
<italic>LINGO1</italic>
(p.S4C, p.V107M, p.A277T, p.R423R, p.G537A, p.D610D) and three in
<italic>LINGO2</italic>
(p.D135D, p.P217P, p.V565V), however segregation analysis did not support pathogenicity. The association study employed 16 tSNPs at the
<italic>LINGO1</italic>
locus and 21 at the
<italic>LINGO2</italic>
locus. One variant in
<italic>LINGO1</italic>
(rs9652490) displayed evidence of an association with ET (odds ratio (OR)=0.63;
<italic>P</italic>
=0.026) and PD (OR=0.54;
<italic>P</italic>
=0.016). Additionally, four other tSNPs in
<italic>LINGO1</italic>
and one in
<italic>LINGO2</italic>
were associated with ET and one tSNP in
<italic>LINGO2</italic>
associated with PD (
<italic>P</italic>
<0.05). Further analysis identified one tSNP in
<italic>LINGO1</italic>
and two in
<italic>LINGO2</italic>
which influenced age at onset of ET and two tSNPs in
<italic>LINGO1</italic>
which altered age at onset of PD (
<italic>P</italic>
<0.05). Our results support a role for
<italic>LINGO1</italic>
and
<italic>LINGO2</italic>
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.</p>
</abstract>
<kwd-group>
<kwd>Essential tremor</kwd>
<kwd>Parkinson disease</kwd>
<kwd>LINGO1</kwd>
<kwd>LINGO2</kwd>
<kwd>Genetic association</kwd>
</kwd-group>
<funding-group>
<award-group>
<funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R01 NS057567 || NS</award-id>
</award-group>
<award-group>
<funding-source country="United States">National Institute on Aging : NIA</funding-source>
<award-id>R01 AG015866 || AG</award-id>
</award-group>
<award-group>
<funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>P50 NS040256 || NS</award-id>
</award-group>
<award-group>
<funding-source country="United States">National Institute on Aging : NIA</funding-source>
<award-id>P01 AG017216 || AG</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>

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   |étape=   Curation
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   |clé=     PMC:3930084
   |texte=   LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease
}}

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HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i   -Sk "pubmed:20369371" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd   \
       | NlmPubMed2Wicri -a JankovicV1
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