Replication of MAPT and SNCA, but not PARK16‐18, as susceptibility genes for Parkinson's disease
Identifieur interne : 000170 ( Main/Exploration ); précédent : 000169; suivant : 000171Replication of MAPT and SNCA, but not PARK16‐18, as susceptibility genes for Parkinson's disease
Auteurs : Ignacio F. Mata [États-Unis] ; Dora Yearout [États-Unis] ; Victoria Alvarez [Espagne] ; Eliecer Coto [Espagne] ; Lorena De Mena [Espagne] ; Renee Ribacoba [Espagne] ; Oswaldo Lorenzo-Betancor [Espagne] ; Lluis Samaranch [Espagne] ; Pau Pastor [Espagne] ; Sebastian Cervantes [Espagne] ; Jon Infante [Espagne] ; Ines Garcia-Gorostiaga [Espagne] ; Maria Sierra [Espagne] ; Onofre Combarros [Espagne] ; Katherine W. Snapinn [États-Unis] ; Karen L. Edwards [États-Unis] ; Cyrus P. Zabetian [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2011-04.
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Abstract
Recent genome‐wide association studies of Parkinson's disease have nominated 3 new susceptibility loci (PARK16‐18) and confirmed 2 known risk genes (MAPT and SNCA) in populations of European ancestry. We sought to replicate these findings. We genotyped single‐nucleotide polymorphisms in each of these genes/loci in 1445 Parkinson's disease patients and 1161 controls from northern Spain. Logistic regression was used to test for association between genotype and Parkinson's disease under an additive model, adjusting for sex, age, and site. We also performed analyses stratified by age at onset. Single‐nucleotide polymorphisms in MAPT (rs1800547; P = 3.1 × 10−4) and SNCA (rs356219; P = 5.5 × 10−4) were significantly associated with Parkinson's disease. However, none of the markers in PARK16‐18 associated with Parkinson's disease in the overall sample, or in any age stratum, with P values ranging from .09 to .88. Although our data further validate MAPT and SNCA as Parkinson's disease susceptibility genes, we failed to replicate PARK16, PARK17, and PARK18. Potential reasons for the discordance between our study and previous genome‐wide association studies include effects of population structure, power, and population‐specific environmental interactions. Our findings suggest that additional studies of PARK16‐18 are necessary to establish the role of these loci in modifying risk for Parkinson's disease in European‐derived populations. © 2011 Movement Disorder Society
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DOI: 10.1002/mds.23642
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xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Alvarez, Victoria" sort="Alvarez, Victoria" uniqKey="Alvarez V" first="Victoria" last="Alvarez">Victoria Alvarez</name><affiliation wicri:level="1"><country xml:lang="fr">Espagne</country><wicri:regionArea>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo</wicri:regionArea><wicri:noRegion>Oviedo</wicri:noRegion></affiliation></author><author><name sortKey="Coto, Eliecer" sort="Coto, Eliecer" uniqKey="Coto E" first="Eliecer" last="Coto">Eliecer Coto</name><affiliation wicri:level="1"><country xml:lang="fr">Espagne</country><wicri:regionArea>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), 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xml:lang="fr">Espagne</country><wicri:regionArea>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander</wicri:regionArea><wicri:noRegion>Santander</wicri:noRegion></affiliation></author><author><name sortKey="Garcia Orostiaga, Ines" sort="Garcia Orostiaga, Ines" uniqKey="Garcia Orostiaga I" first="Ines" last="Garcia-Gorostiaga">Ines Garcia-Gorostiaga</name><affiliation wicri:level="1"><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Service, Hospital de Galdakao, Vizcaya</wicri:regionArea><wicri:noRegion>Vizcaya</wicri:noRegion></affiliation></author><author><name sortKey="Sierra, Maria" sort="Sierra, Maria" uniqKey="Sierra M" first="Maria" last="Sierra">Maria Sierra</name><affiliation wicri:level="1"><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander</wicri:regionArea><wicri:noRegion>Santander</wicri:noRegion></affiliation></author><author><name sortKey="Combarros, Onofre" sort="Combarros, Onofre" uniqKey="Combarros O" first="Onofre" last="Combarros">Onofre Combarros</name><affiliation wicri:level="1"><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander</wicri:regionArea><wicri:noRegion>Santander</wicri:noRegion></affiliation></author><author><name sortKey="Snapinn, Katherine W" sort="Snapinn, Katherine W" uniqKey="Snapinn K" first="Katherine W." last="Snapinn">Katherine W. Snapinn</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Edwards, Karen L" sort="Edwards, Karen L" uniqKey="Edwards K" first="Karen L." last="Edwards">Karen L. Edwards</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-04">2011-04</date><biblScope unit="volume">26</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="819">819</biblScope><biblScope unit="page" to="823">823</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">3EDAAD1E5294BC906AF057DB352374C4B76D4FE8</idno><idno type="DOI">10.1002/mds.23642</idno><idno type="ArticleID">MDS23642</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>genome‐wide</term><term>replication</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Recent genome‐wide association studies of Parkinson's disease have nominated 3 new susceptibility loci (PARK16‐18) and confirmed 2 known risk genes (MAPT and SNCA) in populations of European ancestry. We sought to replicate these findings. We genotyped single‐nucleotide polymorphisms in each of these genes/loci in 1445 Parkinson's disease patients and 1161 controls from northern Spain. Logistic regression was used to test for association between genotype and Parkinson's disease under an additive model, adjusting for sex, age, and site. We also performed analyses stratified by age at onset. Single‐nucleotide polymorphisms in MAPT (rs1800547; P = 3.1 × 10−4) and SNCA (rs356219; P = 5.5 × 10−4) were significantly associated with Parkinson's disease. However, none of the markers in PARK16‐18 associated with Parkinson's disease in the overall sample, or in any age stratum, with P values ranging from .09 to .88. Although our data further validate MAPT and SNCA as Parkinson's disease susceptibility genes, we failed to replicate PARK16, PARK17, and PARK18. Potential reasons for the discordance between our study and previous genome‐wide association studies include effects of population structure, power, and population‐specific environmental interactions. Our findings suggest that additional studies of PARK16‐18 are necessary to establish the role of these loci in modifying risk for Parkinson's disease in European‐derived populations. © 2011 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Espagne</li><li>États-Unis</li></country><region><li>Washington (État)</li></region><settlement><li>Seattle</li></settlement><orgName><li>Université de Washington</li></orgName></list><tree><country name="États-Unis"><region name="Washington (État)"><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F." last="Mata">Ignacio F. Mata</name></region><name sortKey="Edwards, Karen L" sort="Edwards, Karen L" uniqKey="Edwards K" first="Karen L." last="Edwards">Karen L. Edwards</name><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F." last="Mata">Ignacio F. Mata</name><name sortKey="Snapinn, Katherine W" sort="Snapinn, Katherine W" uniqKey="Snapinn K" first="Katherine W." last="Snapinn">Katherine W. Snapinn</name><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name></country><country name="Espagne"><noRegion><name sortKey="Alvarez, Victoria" sort="Alvarez, Victoria" uniqKey="Alvarez V" first="Victoria" last="Alvarez">Victoria Alvarez</name></noRegion><name sortKey="Cervantes, Sebastian" sort="Cervantes, Sebastian" uniqKey="Cervantes S" first="Sebastian" last="Cervantes">Sebastian Cervantes</name><name sortKey="Cervantes, Sebastian" sort="Cervantes, Sebastian" uniqKey="Cervantes S" first="Sebastian" last="Cervantes">Sebastian Cervantes</name><name sortKey="Combarros, Onofre" sort="Combarros, Onofre" uniqKey="Combarros O" first="Onofre" last="Combarros">Onofre Combarros</name><name sortKey="Coto, Eliecer" sort="Coto, Eliecer" uniqKey="Coto E" first="Eliecer" last="Coto">Eliecer Coto</name><name sortKey="De Mena, Lorena" sort="De Mena, Lorena" uniqKey="De Mena L" first="Lorena" last="De Mena">Lorena De Mena</name><name sortKey="Garcia Orostiaga, Ines" sort="Garcia Orostiaga, Ines" uniqKey="Garcia Orostiaga I" first="Ines" last="Garcia-Gorostiaga">Ines Garcia-Gorostiaga</name><name sortKey="Infante, Jon" sort="Infante, Jon" uniqKey="Infante J" first="Jon" last="Infante">Jon Infante</name><name sortKey="Lorenzo Etancor, Oswaldo" sort="Lorenzo Etancor, Oswaldo" uniqKey="Lorenzo Etancor O" first="Oswaldo" last="Lorenzo-Betancor">Oswaldo Lorenzo-Betancor</name><name sortKey="Lorenzo Etancor, Oswaldo" sort="Lorenzo Etancor, Oswaldo" uniqKey="Lorenzo Etancor O" first="Oswaldo" last="Lorenzo-Betancor">Oswaldo Lorenzo-Betancor</name><name sortKey="Pastor, Pau" sort="Pastor, Pau" uniqKey="Pastor P" first="Pau" last="Pastor">Pau Pastor</name><name sortKey="Pastor, Pau" sort="Pastor, Pau" uniqKey="Pastor P" first="Pau" last="Pastor">Pau Pastor</name><name sortKey="Pastor, Pau" sort="Pastor, Pau" uniqKey="Pastor P" first="Pau" last="Pastor">Pau Pastor</name><name sortKey="Ribacoba, Renee" sort="Ribacoba, Renee" uniqKey="Ribacoba R" first="Renee" last="Ribacoba">Renee Ribacoba</name><name sortKey="Samaranch, Lluis" sort="Samaranch, Lluis" uniqKey="Samaranch L" first="Lluis" last="Samaranch">Lluis Samaranch</name><name sortKey="Sierra, Maria" sort="Sierra, Maria" uniqKey="Sierra M" first="Maria" last="Sierra">Maria Sierra</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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