Replication of MAPT and SNCA, but not PARK16‐18, as susceptibility genes for Parkinson's disease
Identifieur interne : 001035 ( Main/Curation ); précédent : 001034; suivant : 001036Replication 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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Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander</wicri:regionArea></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"><mods:affiliation>Neurology Service, Hospital de Galdakao, Vizcaya, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Service, Hospital de Galdakao, Vizcaya</wicri:regionArea></affiliation></author><author><name sortKey="Sierra, Maria" sort="Sierra, Maria" uniqKey="Sierra M" first="Maria" last="Sierra">Maria Sierra</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</mods:affiliation><country 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Snapinn</name><affiliation wicri:level="1"><mods:affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of Washington, Seattle, Washington</wicri:regionArea></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="1"><mods:affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of Washington, Seattle, Washington</wicri:regionArea></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="1"><mods:affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:3EDAAD1E5294BC906AF057DB352374C4B76D4FE8</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1002/mds.23642</idno><idno type="url">https://api.istex.fr/document/3EDAAD1E5294BC906AF057DB352374C4B76D4FE8/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001236</idno><idno type="wicri:Area/Main/Curation">001035</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Replication of MAPT and SNCA, but not PARK16‐18, as susceptibility genes for Parkinson's disease</title><author><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F." last="Mata">Ignacio F. Mata</name><affiliation wicri:level="1"><mods:affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><affiliation wicri:level="1"><mods:affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Alvarez, Victoria" sort="Alvarez, Victoria" uniqKey="Alvarez V" first="Victoria" last="Alvarez">Victoria Alvarez</name><affiliation wicri:level="1"><mods:affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</mods:affiliation><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></affiliation></author><author><name sortKey="Coto, Eliecer" sort="Coto, Eliecer" uniqKey="Coto E" first="Eliecer" last="Coto">Eliecer Coto</name><affiliation wicri:level="1"><mods:affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</mods:affiliation><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></affiliation></author><author><name sortKey="De Mena, Lorena" sort="De Mena, Lorena" uniqKey="De Mena L" first="Lorena" last="De Mena">Lorena De Mena</name><affiliation wicri:level="1"><mods:affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</mods:affiliation><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></affiliation></author><author><name sortKey="Ribacoba, Renee" sort="Ribacoba, Renee" uniqKey="Ribacoba R" first="Renee" last="Ribacoba">Renee Ribacoba</name><affiliation wicri:level="1"><mods:affiliation>Neurology Department, Hospital Alvarez‐Buylla, Mieres, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Department, Hospital Alvarez‐Buylla, Mieres</wicri:regionArea></affiliation></author><author><name sortKey="Lorenzo Etancor, Oswaldo" sort="Lorenzo Etancor, Oswaldo" uniqKey="Lorenzo Etancor O" first="Oswaldo" last="Lorenzo-Betancor">Oswaldo Lorenzo-Betancor</name><affiliation wicri:level="1"><mods:affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona</wicri:regionArea></affiliation></author><author><name sortKey="Samaranch, Lluis" sort="Samaranch, Lluis" uniqKey="Samaranch L" first="Lluis" last="Samaranch">Lluis Samaranch</name><affiliation wicri:level="1"><mods:affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona</wicri:regionArea></affiliation></author><author><name sortKey="Pastor, Pau" sort="Pastor, Pau" uniqKey="Pastor P" first="Pau" last="Pastor">Pau Pastor</name><affiliation wicri:level="1"><mods:affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III</wicri:regionArea></affiliation></author><author><name sortKey="Cervantes, Sebastian" sort="Cervantes, Sebastian" uniqKey="Cervantes S" first="Sebastian" last="Cervantes">Sebastian Cervantes</name><affiliation wicri:level="1"><mods:affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona</wicri:regionArea></affiliation></author><author><name sortKey="Infante, Jon" sort="Infante, Jon" uniqKey="Infante J" first="Jon" last="Infante">Jon Infante</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</mods:affiliation><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></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"><mods:affiliation>Neurology Service, Hospital de Galdakao, Vizcaya, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Neurology Service, Hospital de Galdakao, Vizcaya</wicri:regionArea></affiliation></author><author><name sortKey="Sierra, Maria" sort="Sierra, Maria" uniqKey="Sierra M" first="Maria" last="Sierra">Maria Sierra</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</mods:affiliation><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></affiliation></author><author><name sortKey="Combarros, Onofre" sort="Combarros, Onofre" uniqKey="Combarros O" first="Onofre" last="Combarros">Onofre Combarros</name><affiliation wicri:level="1"><mods:affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</mods:affiliation><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></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="1"><mods:affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of Washington, Seattle, Washington</wicri:regionArea></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="1"><mods:affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, University of Washington, Seattle, Washington</wicri:regionArea></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="1"><mods:affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</mods:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</wicri:regionArea></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></record>Pour manipuler ce document sous Unix (Dilib)
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