AustralieFrV1, Main, Exploration, bibRecord, 005473

An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12

Identifieur interne : 005473 ( Main/Exploration ); précédent : 005472; suivant : 005474

An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12

Auteurs : Bridget H. Maher [Australie] ; Rod A. Lea [Australie] ; Miles Benton [Australie] ; Hannah C. Cox [Australie] ; Claire Bellis [Australie, États-Unis] ; Melanie Carless [États-Unis] ; Thomas D. Dyer [États-Unis] ; Joanne Curran [États-Unis] ; Jac C. Charlesworth [États-Unis, Australie] ; Julie E. Buring [États-Unis] ; Tobias Kurth [États-Unis, Allemagne, France] ; Daniel I. Chasman [États-Unis] ; Paul M. Ridker [États-Unis] ; Markus Schürks [États-Unis, Allemagne] ; John Blangero [États-Unis] ; Lyn R. Griffiths [Australie]

Source :

PLoS ONE [ 1932-6203 ] ; 2012.

RBID : PMC:3362572

Abstract

Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci.

An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1×10⁻⁵) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92×10⁻⁴), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65×10⁻⁴). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women’s Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05).

Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63×10⁻⁵) is located within the 5′UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362572

DOI: 10.1371/journal.pone.0037903
PubMed: 22666411
PubMed Central: 3362572

Affiliations:

Allemagne, Australie, France, États-Unis
Massachusetts, Texas, Île-de-France
Paris

Le document en format XML

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<wicri:regionArea>INSERM Unit 708 - Neuroepidemiology, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I." last="Chasman">Daniel I. Chasman</name>
<affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Division of Preventive Medicine, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Preventive Medicine, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Donald W. Reynolds Center for Cardiovascular Disease Prevention, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Donald W. Reynolds Center for Cardiovascular Disease Prevention, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M." last="Ridker">Paul M. Ridker</name>
<affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Division of Preventive Medicine, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Preventive Medicine, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="aff5"><addr-line>Donald W. Reynolds Center for Cardiovascular Disease Prevention, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Donald W. Reynolds Center for Cardiovascular Disease Prevention, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schurks, Markus" sort="Schurks, Markus" uniqKey="Schurks M" first="Markus" last="Schürks">Markus Schürks</name>
<affiliation wicri:level="2"><nlm:aff id="aff4"><addr-line>Division of Preventive Medicine, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Preventive Medicine, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Department of Neurology, University Hospital Essen, Essen, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurology, University Hospital Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Blangero, John" sort="Blangero, John" uniqKey="Blangero J" first="John" last="Blangero">John Blangero</name>
<affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Griffiths, Lyn R" sort="Griffiths, Lyn R" uniqKey="Griffiths L" first="Lyn R." last="Griffiths">Lyn R. Griffiths</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Genomics Research Centre, Griffith Health Institute, Griffith University, Queensland, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Genomics Research Centre, Griffith Health Institute, Griffith University, Queensland</wicri:regionArea>
<wicri:noRegion>Queensland</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci.</p>
<p>An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1×10<sup>−5</sup>
) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, <italic>P</italic>
 = 8.92×10<sup>−4</sup>
), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, <italic>P</italic>
 = 1.65×10<sup>−4</sup>
). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women’s Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05).</p>
<p>Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63×10<sup>−5</sup>
) is located within the 5′UTR of the <italic>HEPH</italic>
 gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.</p>
</div>
</front>
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</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>France</li>
<li>États-Unis</li>
</country>
<region><li>Massachusetts</li>
<li>Texas</li>
<li>Île-de-France</li>
</region>
<settlement><li>Paris</li>
</settlement>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Maher, Bridget H" sort="Maher, Bridget H" uniqKey="Maher B" first="Bridget H." last="Maher">Bridget H. Maher</name>
</noRegion>
<name sortKey="Bellis, Claire" sort="Bellis, Claire" uniqKey="Bellis C" first="Claire" last="Bellis">Claire Bellis</name>
<name sortKey="Benton, Miles" sort="Benton, Miles" uniqKey="Benton M" first="Miles" last="Benton">Miles Benton</name>
<name sortKey="Charlesworth, Jac C" sort="Charlesworth, Jac C" uniqKey="Charlesworth J" first="Jac C." last="Charlesworth">Jac C. Charlesworth</name>
<name sortKey="Cox, Hannah C" sort="Cox, Hannah C" uniqKey="Cox H" first="Hannah C." last="Cox">Hannah C. Cox</name>
<name sortKey="Griffiths, Lyn R" sort="Griffiths, Lyn R" uniqKey="Griffiths L" first="Lyn R." last="Griffiths">Lyn R. Griffiths</name>
<name sortKey="Lea, Rod A" sort="Lea, Rod A" uniqKey="Lea R" first="Rod A." last="Lea">Rod A. Lea</name>
</country>
<country name="États-Unis"><region name="Texas"><name sortKey="Bellis, Claire" sort="Bellis, Claire" uniqKey="Bellis C" first="Claire" last="Bellis">Claire Bellis</name>
</region>
<name sortKey="Blangero, John" sort="Blangero, John" uniqKey="Blangero J" first="John" last="Blangero">John Blangero</name>
<name sortKey="Buring, Julie E" sort="Buring, Julie E" uniqKey="Buring J" first="Julie E." last="Buring">Julie E. Buring</name>
<name sortKey="Carless, Melanie" sort="Carless, Melanie" uniqKey="Carless M" first="Melanie" last="Carless">Melanie Carless</name>
<name sortKey="Charlesworth, Jac C" sort="Charlesworth, Jac C" uniqKey="Charlesworth J" first="Jac C." last="Charlesworth">Jac C. Charlesworth</name>
<name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I." last="Chasman">Daniel I. Chasman</name>
<name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I." last="Chasman">Daniel I. Chasman</name>
<name sortKey="Curran, Joanne" sort="Curran, Joanne" uniqKey="Curran J" first="Joanne" last="Curran">Joanne Curran</name>
<name sortKey="Dyer, Thomas D" sort="Dyer, Thomas D" uniqKey="Dyer T" first="Thomas D." last="Dyer">Thomas D. Dyer</name>
<name sortKey="Kurth, Tobias" sort="Kurth, Tobias" uniqKey="Kurth T" first="Tobias" last="Kurth">Tobias Kurth</name>
<name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M." last="Ridker">Paul M. Ridker</name>
<name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M." last="Ridker">Paul M. Ridker</name>
<name sortKey="Schurks, Markus" sort="Schurks, Markus" uniqKey="Schurks M" first="Markus" last="Schürks">Markus Schürks</name>
</country>
<country name="Allemagne"><noRegion><name sortKey="Kurth, Tobias" sort="Kurth, Tobias" uniqKey="Kurth T" first="Tobias" last="Kurth">Tobias Kurth</name>
</noRegion>
<name sortKey="Schurks, Markus" sort="Schurks, Markus" uniqKey="Schurks M" first="Markus" last="Schürks">Markus Schürks</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Kurth, Tobias" sort="Kurth, Tobias" uniqKey="Kurth T" first="Tobias" last="Kurth">Tobias Kurth</name>
</region>
</country>
</tree>
</affiliations>
</record>

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   |area=    AustralieFrV1
   |flux=    Main
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   |type=    RBID
   |clé=     PMC:3362572
   |texte=   An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12
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Serveur d'exploration sur les relations entre la France et l'Australie

An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12

An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12

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	Serveur d'exploration sur les relations entre la France et l'Australie
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