Replication of MAPT and SNCA, but not PARK16‐18, as susceptibility genes for Parkinson's disease
Identifieur interne : 001236 ( Main/Corpus ); précédent : 001235; suivant : 001237Replication of MAPT and SNCA, but not PARK16‐18, as susceptibility genes for Parkinson's disease
Auteurs : Ignacio F. Mata ; Dora Yearout ; Victoria Alvarez ; Eliecer Coto ; Lorena De Mena ; Renee Ribacoba ; Oswaldo Lorenzo-Betancor ; Lluis Samaranch ; Pau Pastor ; Sebastian Cervantes ; Jon Infante ; Ines Garcia-Gorostiaga ; Maria Sierra ; Onofre Combarros ; Katherine W. Snapinn ; Karen L. Edwards ; Cyrus P. ZabetianSource :
- 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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Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Infante, Jon" sort="Infante, Jon" uniqKey="Infante J" first="Jon" last="Infante">Jon Infante</name><affiliation><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></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><mods:affiliation>Neurology Service, Hospital de Galdakao, Vizcaya, Spain</mods:affiliation></affiliation></author><author><name sortKey="Sierra, Maria" sort="Sierra, Maria" uniqKey="Sierra M" first="Maria" last="Sierra">Maria Sierra</name><affiliation><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></affiliation></author><author><name sortKey="Combarros, Onofre" sort="Combarros, Onofre" uniqKey="Combarros O" first="Onofre" last="Combarros">Onofre Combarros</name><affiliation><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></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><mods:affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</mods:affiliation></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><mods:affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</mods:affiliation></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><mods:affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</mods:affiliation></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></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><mods:affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><affiliation><mods:affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</mods:affiliation></affiliation></author><author><name sortKey="Alvarez, Victoria" sort="Alvarez, Victoria" uniqKey="Alvarez V" first="Victoria" last="Alvarez">Victoria Alvarez</name><affiliation><mods:affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</mods:affiliation></affiliation></author><author><name sortKey="Coto, Eliecer" sort="Coto, Eliecer" uniqKey="Coto E" first="Eliecer" last="Coto">Eliecer Coto</name><affiliation><mods:affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</mods:affiliation></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><mods:affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</mods:affiliation></affiliation></author><author><name sortKey="Ribacoba, Renee" sort="Ribacoba, Renee" uniqKey="Ribacoba R" first="Renee" last="Ribacoba">Renee Ribacoba</name><affiliation><mods:affiliation>Neurology Department, Hospital Alvarez‐Buylla, Mieres, Spain</mods:affiliation></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><mods:affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Samaranch, Lluis" sort="Samaranch, Lluis" uniqKey="Samaranch L" first="Lluis" last="Samaranch">Lluis Samaranch</name><affiliation><mods:affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Pastor, Pau" sort="Pastor, Pau" uniqKey="Pastor P" first="Pau" last="Pastor">Pau Pastor</name><affiliation><mods:affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain</mods:affiliation></affiliation></author><author><name sortKey="Cervantes, Sebastian" sort="Cervantes, Sebastian" uniqKey="Cervantes S" first="Sebastian" last="Cervantes">Sebastian Cervantes</name><affiliation><mods:affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Infante, Jon" sort="Infante, Jon" uniqKey="Infante J" first="Jon" last="Infante">Jon Infante</name><affiliation><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></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><mods:affiliation>Neurology Service, Hospital de Galdakao, Vizcaya, Spain</mods:affiliation></affiliation></author><author><name sortKey="Sierra, Maria" sort="Sierra, Maria" uniqKey="Sierra M" first="Maria" last="Sierra">Maria Sierra</name><affiliation><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></affiliation></author><author><name sortKey="Combarros, Onofre" sort="Combarros, Onofre" uniqKey="Combarros O" first="Onofre" last="Combarros">Onofre Combarros</name><affiliation><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></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><mods:affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</mods:affiliation></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><mods:affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</mods:affiliation></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><mods:affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</mods:affiliation></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><istex><corpusName>wiley</corpusName><author><json:item><name>Ignacio F. Mata PhD</name><affiliations><json:string>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</json:string><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</json:string></affiliations></json:item><json:item><name>Dora Yearout BS</name><affiliations><json:string>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</json:string><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</json:string></affiliations></json:item><json:item><name>Victoria Alvarez PhD</name><affiliations><json:string>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</json:string></affiliations></json:item><json:item><name>Eliecer Coto PhD</name><affiliations><json:string>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</json:string></affiliations></json:item><json:item><name>Lorena de Mena BS</name><affiliations><json:string>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</json:string></affiliations></json:item><json:item><name>Renee Ribacoba MD</name><affiliations><json:string>Neurology Department, Hospital Alvarez‐Buylla, Mieres, Spain</json:string></affiliations></json:item><json:item><name>Oswaldo Lorenzo‐Betancor MD</name><affiliations><json:string>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</json:string><json:string>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</json:string></affiliations></json:item><json:item><name>Lluis Samaranch PhD</name><affiliations><json:string>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</json:string></affiliations></json:item><json:item><name>Pau Pastor MD, PhD</name><affiliations><json:string>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</json:string><json:string>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</json:string><json:string>CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain</json:string></affiliations></json:item><json:item><name>Sebastian Cervantes MD</name><affiliations><json:string>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</json:string><json:string>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</json:string></affiliations></json:item><json:item><name>Jon Infante MD</name><affiliations><json:string>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</json:string></affiliations></json:item><json:item><name>Ines Garcia‐Gorostiaga MD</name><affiliations><json:string>Neurology Service, Hospital de Galdakao, Vizcaya, Spain</json:string></affiliations></json:item><json:item><name>Maria Sierra MD</name><affiliations><json:string>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</json:string></affiliations></json:item><json:item><name>Onofre Combarros MD</name><affiliations><json:string>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</json:string></affiliations></json:item><json:item><name>Katherine W. Snapinn MS</name><affiliations><json:string>Department of Epidemiology, University of Washington, Seattle, Washington, USA</json:string></affiliations></json:item><json:item><name>Karen L. Edwards PhD</name><affiliations><json:string>Department of Epidemiology, University of Washington, Seattle, Washington, USA</json:string></affiliations></json:item><json:item><name>Cyrus P. Zabetian MD, MS</name><affiliations><json:string>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</json:string><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genome‐wide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>replication</value></json:item></subject><articleId><json:string>MDS23642</json:string></articleId><language><json:string>eng</json:string></language><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</abstract><qualityIndicators><score>5.537</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>3</keywordCount><abstractCharCount>1481</abstractCharCount><pdfWordCount>2981</pdfWordCount><pdfCharCount>19592</pdfCharCount><pdfPageCount>5</pdfPageCount><abstractWordCount>213</abstractWordCount></qualityIndicators><title>Replication of MAPT and SNCA, but not PARK16‐18, as susceptibility genes for Parkinson's disease</title><genre><json:string>article</json:string></genre><host><volume>26</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>5</total><last>823</last><first>819</first></pages><issn><json:string>0885-3185</json:string></issn><issue>5</issue><subject><json:item><value>Research Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8257</json:string></eissn><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1002/mds.23642</json:string></doi><id>3EDAAD1E5294BC906AF057DB352374C4B76D4FE8</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/3EDAAD1E5294BC906AF057DB352374C4B76D4FE8/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/3EDAAD1E5294BC906AF057DB352374C4B76D4FE8/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/3EDAAD1E5294BC906AF057DB352374C4B76D4FE8/fulltext/tei"><teiHeader><fileDesc><titleStmt><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></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2011</date></publicationStmt><notesStmt><note type="content">*Relevant conflict of interest/financial disclosures: Nothing to report. This work was supported by funding from the Department of Veterans Affairs (1I01BX000531), National Institutes of Health (P50 NS062684 and R01 NS065070), Spanish Ministry of Education and Science (SAF2006‐10126: 2006‐2009), Fondo de Investigacion Sanitaria (FIS, PI070014), Spanish Ministry of Science and Technology, European Social Fund, and the Asociación Parkinson Asturias. Full financial disclosures and author roles may be found in the online version of this article.</note></notesStmt><sourceDesc><biblStruct type="inbook"><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><persName><forename type="first">Ignacio F.</forename><surname>Mata</surname></persName><roleName type="degree">PhD</roleName><affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</affiliation><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</affiliation></author><author><persName><forename type="first">Dora</forename><surname>Yearout</surname></persName><roleName type="degree">BS</roleName><affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</affiliation><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</affiliation></author><author><persName><forename type="first">Victoria</forename><surname>Alvarez</surname></persName><roleName type="degree">PhD</roleName><affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</affiliation></author><author><persName><forename type="first">Eliecer</forename><surname>Coto</surname></persName><roleName type="degree">PhD</roleName><affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</affiliation></author><author><persName><forename type="first">Lorena</forename><surname>de Mena</surname></persName><roleName type="degree">BS</roleName><affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</affiliation></author><author><persName><forename type="first">Renee</forename><surname>Ribacoba</surname></persName><roleName type="degree">MD</roleName><affiliation>Neurology Department, Hospital Alvarez‐Buylla, Mieres, Spain</affiliation></author><author><persName><forename type="first">Oswaldo</forename><surname>Lorenzo‐Betancor</surname></persName><roleName type="degree">MD</roleName><affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</affiliation><affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</affiliation></author><author><persName><forename type="first">Lluis</forename><surname>Samaranch</surname></persName><roleName type="degree">PhD</roleName><affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</affiliation></author><author><persName><forename type="first">Pau</forename><surname>Pastor</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</affiliation><affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</affiliation><affiliation>CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain</affiliation></author><author><persName><forename type="first">Sebastian</forename><surname>Cervantes</surname></persName><roleName type="degree">MD</roleName><affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</affiliation><affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</affiliation></author><author><persName><forename type="first">Jon</forename><surname>Infante</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</affiliation></author><author><persName><forename type="first">Ines</forename><surname>Garcia‐Gorostiaga</surname></persName><roleName type="degree">MD</roleName><affiliation>Neurology Service, Hospital de Galdakao, Vizcaya, Spain</affiliation></author><author><persName><forename type="first">Maria</forename><surname>Sierra</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</affiliation></author><author><persName><forename type="first">Onofre</forename><surname>Combarros</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</affiliation></author><author><persName><forename type="first">Katherine W.</forename><surname>Snapinn</surname></persName><roleName type="degree">MS</roleName><affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</affiliation></author><author><persName><forename type="first">Karen L.</forename><surname>Edwards</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</affiliation></author><author><persName><forename type="first">Cyrus P.</forename><surname>Zabetian</surname></persName><roleName type="degree">MD, MS</roleName><note type="correspondence"><p>Correspondence: Geriatric Research Education and Clinical Center S‐182, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA</p></note><affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</affiliation><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="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></monogr><idno type="istex">3EDAAD1E5294BC906AF057DB352374C4B76D4FE8</idno><idno type="DOI">10.1002/mds.23642</idno><idno type="ArticleID">MDS23642</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>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</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>genome‐wide</term></item><item><term>replication</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-11-16">Received</change><change when="2010-12-27">Registration</change><change when="2011-04">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/3EDAAD1E5294BC906AF057DB352374C4B76D4FE8/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="50"><doi origin="wiley" registered="yes">10.1002/mds.v26.5</doi><numberingGroup><numbering type="journalVolume" number="26">26</numbering><numbering type="journalIssue">5</numbering></numberingGroup><coverDate startDate="2011-04">April 2011</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="110" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.23642</doi><idGroup><id type="unit" value="MDS23642"></id></idGroup><countGroup><count type="pageTotal" number="5"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2011 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2010-11-16"></event><event type="manuscriptRevised" date="2010-12-17"></event><event type="manuscriptAccepted" date="2010-12-27"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.5.2 mode:FullText" date="2011-07-19"></event><event type="publishedOnlineEarlyUnpaginated" date="2011-03-21"></event><event type="publishedOnlineFinalForm" date="2011-04-21"></event><event type="firstOnline" date="2011-03-21"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-31"></event></eventGroup><numberingGroup><numbering type="pageFirst">819</numbering><numbering type="pageLast">823</numbering></numberingGroup><correspondenceTo>Geriatric Research Education and Clinical Center S‐182, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS23642.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="22"></count><count type="wordTotal" number="4515"></count></countGroup><titleGroup><title type="main" xml:lang="en">Replication of <i>MAPT</i> and <i>SNCA</i>, but not <i>PARK16‐18</i>, as susceptibility genes for Parkinson's disease<link href="#fn1"></link></title><title type="short" xml:lang="en"><fi>SNCA</fi>, <fi>MAPT</fi>, <fi>PARK16‐18</fi> IN PD Susceptibility</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Ignacio F.</givenNames><familyName>Mata</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Dora</givenNames><familyName>Yearout</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Victoria</givenNames><familyName>Alvarez</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Eliecer</givenNames><familyName>Coto</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Lorena</givenNames><familyName>de Mena</familyName><degrees>BS</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Renee</givenNames><familyName>Ribacoba</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af5 #af6"><personName><givenNames>Oswaldo</givenNames><familyName>Lorenzo‐Betancor</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Lluis</givenNames><familyName>Samaranch</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af5 #af6 #af7"><personName><givenNames>Pau</givenNames><familyName>Pastor</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af5 #af6"><personName><givenNames>Sebastian</givenNames><familyName>Cervantes</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Jon</givenNames><familyName>Infante</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af9"><personName><givenNames>Ines</givenNames><familyName>Garcia‐Gorostiaga</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Maria</givenNames><familyName>Sierra</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Onofre</givenNames><familyName>Combarros</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au15" creatorRole="author" affiliationRef="#af10"><personName><givenNames>Katherine W.</givenNames><familyName>Snapinn</familyName><degrees>MS</degrees></personName></creator><creator xml:id="au16" creatorRole="author" affiliationRef="#af10"><personName><givenNames>Karen L.</givenNames><familyName>Edwards</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au17" creatorRole="author" affiliationRef="#af1 #af2" corresponding="yes"><personName><givenNames>Cyrus P.</givenNames><familyName>Zabetian</familyName><degrees>MD, MS</degrees></personName><contactDetails><email>zabetian@u.washington.edu</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="ES" type="organization"><unparsedAffiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="ES" 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Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="ES" type="organization"><unparsedAffiliation>Neurology Service, Hospital de Galdakao, Vizcaya, Spain</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="US" type="organization"><unparsedAffiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">genome‐wide</keyword><keyword xml:id="kwd3">replication</keyword></keywordGroup><supportingInformation><p> Additional Supporting Information may be found in the online version of this article. </p><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23642:MDS_23642_sm_supptable1"></mediaResource><caption>Supporting Table 1</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:08853185:media:mds23642:MDS_23642_sm_authorroles"></mediaResource><caption>Author Roles and Disclosures</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Recent genome‐wide association studies of Parkinson's disease have nominated 3 new susceptibility loci (<i>PARK16</i>‐<i>18</i>) and confirmed 2 known risk genes (<i>MAPT</i> and <i>SNCA</i>) 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 <i>MAPT</i> (rs1800547; <i>P</i> = 3.1 × 10<sup>−4</sup>) and <i>SNCA</i> (rs356219; <i>P</i> = 5.5 × 10<sup>−4</sup>) were significantly associated with Parkinson's disease. However, none of the markers in <i>PARK16‐18</i> associated with Parkinson's disease in the overall sample, or in any age stratum, with <i>P</i> values ranging from .09 to .88. Although our data further validate <i>MAPT</i> and <i>SNCA</i> as Parkinson's disease susceptibility genes, we failed to replicate <i>PARK16</i>, <i>PARK17</i>, and <i>PARK18</i>. 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 <i>PARK16‐18</i> are necessary to establish the role of these loci in modifying risk for Parkinson's disease in European‐derived populations. © 2011 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p><b>Relevant conflict of interest/financial disclosures:</b> Nothing to report.</p><p>This work was supported by funding from the Department of Veterans Affairs (1I01BX000531), National Institutes of Health (P50 NS062684 and R01 NS065070), Spanish Ministry of Education and Science (SAF2006‐10126: 2006‐2009), Fondo de Investigacion Sanitaria (FIS, PI070014), Spanish Ministry of Science and Technology, European Social Fund, and the Asociación Parkinson Asturias.</p><p>Full financial disclosures and author roles may be found in the online version of this article.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo 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Washington, USA</affiliation><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Victoria</namePart><namePart type="family">Alvarez</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eliecer</namePart><namePart type="family">Coto</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lorena</namePart><namePart type="family">de Mena</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSINFRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Renee</namePart><namePart type="family">Ribacoba</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neurology Department, Hospital Alvarez‐Buylla, Mieres, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Oswaldo</namePart><namePart type="family">Lorenzo‐Betancor</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</affiliation><affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lluis</namePart><namePart type="family">Samaranch</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Pau</namePart><namePart type="family">Pastor</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</affiliation><affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</affiliation><affiliation>CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sebastian</namePart><namePart type="family">Cervantes</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain</affiliation><affiliation>Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jon</namePart><namePart type="family">Infante</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ines</namePart><namePart type="family">Garcia‐Gorostiaga</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neurology Service, Hospital de Galdakao, Vizcaya, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maria</namePart><namePart type="family">Sierra</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Onofre</namePart><namePart type="family">Combarros</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), “Marques de Valdecilla” University Hospital, Santander, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Katherine W.</namePart><namePart type="family">Snapinn</namePart><namePart type="termsOfAddress">MS</namePart><affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karen L.</namePart><namePart type="family">Edwards</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Epidemiology, University of Washington, Seattle, Washington, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cyrus P.</namePart><namePart type="family">Zabetian</namePart><namePart type="termsOfAddress">MD, MS</namePart><affiliation>Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA</affiliation><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA</affiliation><description>Correspondence: Geriatric Research Education and Clinical Center S‐182, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-04</dateIssued><dateCaptured encoding="w3cdtf">2010-11-16</dateCaptured><dateValid encoding="w3cdtf">2010-12-27</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="tables">2</extent><extent unit="references">22</extent><extent unit="words">4515</extent></physicalDescription><abstract 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</abstract><note type="content">*Relevant conflict of interest/financial disclosures: Nothing to report. This work was supported by funding from the Department of Veterans Affairs (1I01BX000531), National Institutes of Health (P50 NS062684 and R01 NS065070), Spanish Ministry of Education and Science (SAF2006‐10126: 2006‐2009), Fondo de Investigacion Sanitaria (FIS, PI070014), Spanish Ministry of Science and Technology, European Social Fund, and the Asociación Parkinson Asturias. Full financial disclosures and author roles may be found in the online version of this article.</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>genome‐wide</topic><topic>replication</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><genre type="Journal">journal</genre><note type="content"> Additional Supporting Information may be found in the online version of this article.Supporting Info Item: Supporting Table 1 - Author Roles and Disclosures - </note><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>26</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>819</start><end>823</end><total>5</total></extent></part></relatedItem><identifier type="istex">3EDAAD1E5294BC906AF057DB352374C4B76D4FE8</identifier><identifier type="DOI">10.1002/mds.23642</identifier><identifier type="ArticleID">MDS23642</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2011 Movement Disorder Society</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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