MovDisordV3, Pmc, Curation, bibRecord, 000187

Genomewide linkage study of modifiers of LRRK2-related Parkinson’s disease

Identifieur interne : 000187 ( Pmc/Curation ); précédent : 000186; suivant : 000188

Genomewide linkage study of modifiers of LRRK2-related Parkinson’s disease

Auteurs : Jeanne C. Latourelle [États-Unis] ; Audrey E. Hendricks [États-Unis] ; Nathan Pankratz [États-Unis] ; Jemma B. Wilk [États-Unis] ; Cheryl Halter [États-Unis] ; William C. Nichols ; James F. Gusella [États-Unis] ; Anita L. Destefano [États-Unis] ; Richard H. Myers [États-Unis] ; Tatiana Foroud [États-Unis]

Source :

Movement Disorders [ 0885-3185 ] ; 2011.

RBID : PMC:3346677

Abstract

Background

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2), located at 12q12, are the most common known genetic causes of Parkinson’s disease (PD). Studies of LRRK2 mutation carriers have shown incomplete and age-dependent penetrance and previous studies have suggested that inherited susceptibility factors may modify the penetrance of LRRK2 mutations.

Methods

Genomewide linkage to age of onset of LRRK2-related PD was evaluated in a sample of 113 LRRK2 mutation carriers from 64 families using single nucleotide polymorphism data from the Illumina HumanCNV370 genotyping array. Association between onset age and SNPs located under suggestive linkage peaks was also evaluated.

Results

The top LOD-score for onset age (LOD-score=2.43) was located in the chromosome 1q32.1 region. Moderate linkage to onset was also identified at 16q12.1 (LOD-score=1.58). Examination of single nucleotide polymorphism association to PD onset under the linkage peaks revealed no statistically significant SNP associations.

Conclusions

The two novel genomic regions identified may harbor modifiers of LRRK2-related PD onset age or penetrance and further study of these regions may provide important insight into LRRK2-related PD.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346677

DOI: 10.1002/mds.23781
PubMed: 21661047
PubMed Central: 3346677

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William C. Nichols

<affiliation><nlm:aff id="A4">Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, 45229</nlm:aff>
<wicri:noCountry code="subfield">45229</wicri:noCountry>
</affiliation>

Le document en format XML

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-related Parkinson’s disease</title>
<author><name sortKey="Latourelle, Jeanne C" sort="Latourelle, Jeanne C" uniqKey="Latourelle J" first="Jeanne C." last="Latourelle">Jeanne C. Latourelle</name>
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<placeName><region type="state">Indiana</region>
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<wicri:noCountry code="subfield">45229</wicri:noCountry>
</affiliation>
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<author><name sortKey="Gusella, James F" sort="Gusella, James F" uniqKey="Gusella J" first="James F." last="Gusella">James F. Gusella</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Destefano, Anita L" sort="Destefano, Anita L" uniqKey="Destefano A" first="Anita L." last="Destefano">Anita L. Destefano</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
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<author><name sortKey="Myers, Richard H" sort="Myers, Richard H" uniqKey="Myers R" first="Richard H." last="Myers">Richard H. Myers</name>
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<author><name sortKey="Foroud, Tatiana" sort="Foroud, Tatiana" uniqKey="Foroud T" first="Tatiana" last="Foroud">Tatiana Foroud</name>
<affiliation wicri:level="2"><nlm:aff id="A3">Indiana University School of Medicine, Indianapolis, IN 46202</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Indiana</region>
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<series><title level="j">Movement Disorders</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2011">2011</date>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">Mutations in the leucine-rich repeat kinase 2 gene (<italic>LRRK2</italic>
), located at 12q12, are the most common known genetic causes of Parkinson’s disease (PD). Studies of <italic>LRRK2</italic>
 mutation carriers have shown incomplete and age-dependent penetrance and previous studies have suggested that inherited susceptibility factors may modify the penetrance of <italic>LRRK2</italic>
 mutations.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">Genomewide linkage to age of onset of <italic>LRRK2</italic>
-related PD was evaluated in a sample of 113 <italic>LRRK2</italic>
 mutation carriers from 64 families using single nucleotide polymorphism data from the Illumina HumanCNV370 genotyping array. Association between onset age and SNPs located under suggestive linkage peaks was also evaluated.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">The top LOD-score for onset age (LOD-score=2.43) was located in the chromosome 1q32.1 region. Moderate linkage to onset was also identified at 16q12.1 (LOD-score=1.58). Examination of single nucleotide polymorphism association to PD onset under the linkage peaks revealed no statistically significant SNP associations.</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">The two novel genomic regions identified may harbor modifiers of <italic>LRRK2</italic>
-related PD onset age or penetrance and further study of these regions may provide important insight into <italic>LRRK2</italic>
-related PD.</p>
</sec>
</div>
</front>
</TEI>
<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">8610688</journal-id>
<journal-id journal-id-type="pubmed-jr-id">5937</journal-id>
<journal-id journal-id-type="nlm-ta">Mov Disord</journal-id>
<journal-id journal-id-type="iso-abbrev">Mov. Disord.</journal-id>
<journal-title-group><journal-title>Movement Disorders</journal-title>
</journal-title-group>
<issn pub-type="ppub">0885-3185</issn>
<issn pub-type="epub">1531-8257</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21661047</article-id>
<article-id pub-id-type="pmc">3346677</article-id>
<article-id pub-id-type="doi">10.1002/mds.23781</article-id>
<article-id pub-id-type="manuscript">NIHMS289008</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Genomewide linkage study of modifiers of <italic>LRRK2</italic>
-related Parkinson’s disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>LATOURELLE</surname>
<given-names>JEANNE C.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>HENDRICKS</surname>
<given-names>AUDREY E.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>PANKRATZ</surname>
<given-names>NATHAN</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>WILK</surname>
<given-names>JEMMA B.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>HALTER</surname>
<given-names>CHERYL</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>NICHOLS</surname>
<given-names>WILLIAM C.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>GUSELLA</surname>
<given-names>JAMES F.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>DESTEFANO</surname>
<given-names>ANITA L.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>MYERS</surname>
<given-names>RICHARD H.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>FOROUD</surname>
<given-names>TATIANA</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<on-behalf-of>THE PSG – PROGENI AND GENEPD INVESTIGATORS, COORDINATORS AND MOLECULAR GENETIC LABORATORIES</on-behalf-of>
</contrib-group>
<aff id="A1"><label>1</label>
Boston University School of Medicine, Boston, MA 02118</aff>
<aff id="A2"><label>2</label>
Boston University School of Public Health, Boston, MA 02118</aff>
<aff id="A3"><label>3</label>
Indiana University School of Medicine, Indianapolis, IN 46202</aff>
<aff id="A4"><label>4</label>
Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, 45229</aff>
<aff id="A5"><label>5</label>
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114</aff>
<author-notes><corresp id="FN1">Corresponding Author: Jeanne Latourelle, 72 East Concord St, B-617, Boston MA, 02119, phone: 617-414-1199, fax: 617-638-8086, <email>jlatoure@bu.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>23</day>
<month>4</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>09</day>
<month>6</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><month>9</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>9</month>
<year>2012</year>
</pub-date>
<volume>26</volume>
<issue>11</issue>
<fpage>2039</fpage>
<lpage>2044</lpage>
<abstract><sec id="S1"><title>Background</title>
<p id="P1">Mutations in the leucine-rich repeat kinase 2 gene (<italic>LRRK2</italic>
), located at 12q12, are the most common known genetic causes of Parkinson’s disease (PD). Studies of <italic>LRRK2</italic>
 mutation carriers have shown incomplete and age-dependent penetrance and previous studies have suggested that inherited susceptibility factors may modify the penetrance of <italic>LRRK2</italic>
 mutations.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">Genomewide linkage to age of onset of <italic>LRRK2</italic>
-related PD was evaluated in a sample of 113 <italic>LRRK2</italic>
 mutation carriers from 64 families using single nucleotide polymorphism data from the Illumina HumanCNV370 genotyping array. Association between onset age and SNPs located under suggestive linkage peaks was also evaluated.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">The top LOD-score for onset age (LOD-score=2.43) was located in the chromosome 1q32.1 region. Moderate linkage to onset was also identified at 16q12.1 (LOD-score=1.58). Examination of single nucleotide polymorphism association to PD onset under the linkage peaks revealed no statistically significant SNP associations.</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">The two novel genomic regions identified may harbor modifiers of <italic>LRRK2</italic>
-related PD onset age or penetrance and further study of these regions may provide important insight into <italic>LRRK2</italic>
-related PD.</p>
</sec>
</abstract>
<kwd-group><kwd>Parkinson’s Disease</kwd>
<kwd>LRRK2</kwd>
<kwd>Linkage</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 NS037167-10S2 || NS</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R01 NS036711-09 || NS</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>

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Movement Disorders (revue)

Genomewide linkage study of modifiers of LRRK2-related Parkinson’s disease

Genomewide linkage study of modifiers of LRRK2-related Parkinson’s disease

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