Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease
Identifieur interne : 000B98 ( Main/Exploration ); précédent : 000B97; suivant : 000B99Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease
Auteurs : Yonghong Li [États-Unis] ; Andrew Grupe [États-Unis] ; Charles Rowland [États-Unis] ; Peter Holmans ; Ricardo Segurado ; Richard Abraham ; Lesley Jones ; Joseph Catanese [États-Unis] ; David Ross [États-Unis] ; Kevin Mayo ; Maribel Martinez ; Paul Hollingworth ; Alison Goate ; Nigel J. Cairns ; Brad A. Racette ; Joel S. Perlmutter ; Michael C. O'Donovan ; John C. Morris ; Carol Brayne ; David C. Rubinsztein ; Simon Lovestone ; Leon J. Thal ; Michael J. Owen ; Julie WilliamsSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2008-03-01.
Abstract
Late-onset Alzheimer's disease (LOAD) and Parkinson's disease (PD) are the most common neurodegenerative disorders and in both diseases susceptibility is known to be influenced by genes. We set out to identify novel susceptibility genes for LOAD by performing a large scale, multi-tiered association study testing 4692 single nucleotide polymorphism (SNPs). We identified a SNP within a putative transcription factor binding site in the NEDD9 gene (neural precursor cell expressed, developmentally down-regulated), that shows good evidence of association with disease risk in four out of five LOAD samples [N 3521, P 5.38106, odds ratio (OR) 1.38 (1.201.59)] and in addition, we observed a similar pattern of association in two PD sample sets [N 1464, P 0.0145, OR 1.31 (1.051.62)]. In exploring a potential mechanism for the association, we observed that expression of NEDD9 and APOE show a strong inverse correlation in the hippocampus of Alzheimer's cases. These data implicate NEDD9 as a novel susceptibility gene for LOAD and possibly PD.
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DOI: 10.1093/hmg/ddm348
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Rubinsztein</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Lovestone, Simon" sort="Lovestone, Simon" uniqKey="Lovestone S" first="Simon" last="Lovestone">Simon Lovestone</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Thal, Leon J" sort="Thal, Leon J" uniqKey="Thal L" first="Leon J." last="Thal">Leon J. Thal</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Owen, Michael J" sort="Owen, Michael J" uniqKey="Owen M" first="Michael J." last="Owen">Michael J. Owen</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author><author><name sortKey="Williams, Julie" sort="Williams, Julie" uniqKey="Williams J" first="Julie" last="Williams">Julie Williams</name><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2008-03-01">2008-03-01</date><biblScope unit="volume">17</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="759">759</biblScope><biblScope unit="page" to="767">767</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">967326C79917770D07F993B73F9E48B7E088EE16</idno><idno type="DOI">10.1093/hmg/ddm348</idno><idno type="ArticleID">ddm348</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Late-onset Alzheimer's disease (LOAD) and Parkinson's disease (PD) are the most common neurodegenerative disorders and in both diseases susceptibility is known to be influenced by genes. We set out to identify novel susceptibility genes for LOAD by performing a large scale, multi-tiered association study testing 4692 single nucleotide polymorphism (SNPs). We identified a SNP within a putative transcription factor binding site in the NEDD9 gene (neural precursor cell expressed, developmentally down-regulated), that shows good evidence of association with disease risk in four out of five LOAD samples [N 3521, P 5.38106, odds ratio (OR) 1.38 (1.201.59)] and in addition, we observed a similar pattern of association in two PD sample sets [N 1464, P 0.0145, OR 1.31 (1.051.62)]. In exploring a potential mechanism for the association, we observed that expression of NEDD9 and APOE show a strong inverse correlation in the hippocampus of Alzheimer's cases. These data implicate NEDD9 as a novel susceptibility gene for LOAD and possibly PD.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><noCountry><name sortKey="Abraham, Richard" sort="Abraham, Richard" uniqKey="Abraham R" first="Richard" last="Abraham">Richard Abraham</name><name sortKey="Brayne, Carol" sort="Brayne, Carol" uniqKey="Brayne C" first="Carol" last="Brayne">Carol Brayne</name><name sortKey="Cairns, Nigel J" sort="Cairns, Nigel J" uniqKey="Cairns N" first="Nigel J." last="Cairns">Nigel J. Cairns</name><name sortKey="Goate, Alison" sort="Goate, Alison" uniqKey="Goate A" first="Alison" last="Goate">Alison Goate</name><name sortKey="Hollingworth, Paul" sort="Hollingworth, Paul" uniqKey="Hollingworth P" first="Paul" last="Hollingworth">Paul Hollingworth</name><name sortKey="Holmans, Peter" sort="Holmans, Peter" uniqKey="Holmans P" first="Peter" last="Holmans">Peter Holmans</name><name sortKey="Jones, Lesley" sort="Jones, Lesley" uniqKey="Jones L" first="Lesley" last="Jones">Lesley Jones</name><name sortKey="Lovestone, Simon" sort="Lovestone, Simon" uniqKey="Lovestone S" first="Simon" last="Lovestone">Simon Lovestone</name><name sortKey="Martinez, Maribel" sort="Martinez, Maribel" uniqKey="Martinez M" first="Maribel" last="Martinez">Maribel Martinez</name><name sortKey="Mayo, Kevin" sort="Mayo, Kevin" uniqKey="Mayo K" first="Kevin" last="Mayo">Kevin Mayo</name><name sortKey="Morris, John C" sort="Morris, John C" uniqKey="Morris J" first="John C." last="Morris">John C. Morris</name><name sortKey="O Donovan, Michael C" sort="O Donovan, Michael C" uniqKey="O Donovan M" first="Michael C." last="O'Donovan">Michael C. O'Donovan</name><name sortKey="Owen, Michael J" sort="Owen, Michael J" uniqKey="Owen M" first="Michael J." last="Owen">Michael J. Owen</name><name sortKey="Perlmutter, Joel S" sort="Perlmutter, Joel S" uniqKey="Perlmutter J" first="Joel S." last="Perlmutter">Joel S. Perlmutter</name><name sortKey="Racette, Brad A" sort="Racette, Brad A" uniqKey="Racette B" first="Brad A." last="Racette">Brad A. Racette</name><name sortKey="Rubinsztein, David C" sort="Rubinsztein, David C" uniqKey="Rubinsztein D" first="David C." last="Rubinsztein">David C. Rubinsztein</name><name sortKey="Segurado, Ricardo" sort="Segurado, Ricardo" uniqKey="Segurado R" first="Ricardo" last="Segurado">Ricardo Segurado</name><name sortKey="Thal, Leon J" sort="Thal, Leon J" uniqKey="Thal L" first="Leon J." last="Thal">Leon J. Thal</name><name sortKey="Williams, Julie" sort="Williams, Julie" uniqKey="Williams J" first="Julie" last="Williams">Julie Williams</name></noCountry><country name="États-Unis"><region name="Californie"><name sortKey="Li, Yonghong" sort="Li, Yonghong" uniqKey="Li Y" first="Yonghong" last="Li">Yonghong Li</name></region><name sortKey="Catanese, Joseph" sort="Catanese, Joseph" uniqKey="Catanese J" first="Joseph" last="Catanese">Joseph Catanese</name><name sortKey="Grupe, Andrew" sort="Grupe, Andrew" uniqKey="Grupe A" first="Andrew" last="Grupe">Andrew Grupe</name><name sortKey="Ross, David" sort="Ross, David" uniqKey="Ross D" first="David" last="Ross">David Ross</name><name sortKey="Rowland, Charles" sort="Rowland, Charles" uniqKey="Rowland C" first="Charles" last="Rowland">Charles Rowland</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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