Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study
Identifieur interne : 001645 ( Main/Corpus ); précédent : 001644; suivant : 001646Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study
Auteurs : Evangelos Evangelou ; Demetrius M. Maraganore ; Grazia Annesi ; Laura Brighina ; Alexis Brice ; Alexis Elbaz ; Carlo Ferrarese ; Georgios M. Hadjigeorgiou ; Rejko Krueger ; Jean-Charles Lambert ; Suzanne Lesage ; Katerina Markopoulou ; George D. Mellick ; Bram Meeus ; Nancy L. Pedersen ; Aldo Quattrone ; Christine Van Broeckhoven ; Manu Sharma ; Peter A. Silburn ; Eng-King Tan ; Karin Wirdefeldt ; John P. A. IoannidisSource :
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics [ 1552-4841 ] ; 2010-01.
English descriptors
Abstract
Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta‐analysis of the first two GWA investigations might be replicable in different populations. We examined six single‐nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the “Genetic Epidemiology of Parkinson's Disease” (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98–1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques. © 2009 Wiley‐Liss, Inc.
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DOI: 10.1002/ajmg.b.30980
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Mellick</name><affiliation><mods:affiliation>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</mods:affiliation></affiliation></author><author><name sortKey="Meeus, Bram" sort="Meeus, Bram" uniqKey="Meeus B" first="Bram" last="Meeus">Bram Meeus</name><affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>University of Antwerp, Antwerpen, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Pedersen, Nancy L" sort="Pedersen, Nancy L" uniqKey="Pedersen N" first="Nancy L." last="Pedersen">Nancy L. Pedersen</name><affiliation><mods:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name><affiliation><mods:affiliation>Institute of Neurology, University Magna Graecia, Catanzaro, Italy</mods:affiliation></affiliation></author><author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>University of Antwerp, Antwerpen, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><affiliation><mods:affiliation>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name><affiliation><mods:affiliation>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</mods:affiliation></affiliation></author><author><name sortKey="Tan, Eng Ing" sort="Tan, Eng Ing" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name><affiliation><mods:affiliation>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Duke‐NUS Graduate Medical School, Singapore, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><affiliation><mods:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P. A." last="Ioannidis">John P. A. Ioannidis</name><affiliation><mods:affiliation>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Biomedical Research Institute, Foundation for Research and Technology‐Hellas, Ioannina, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:68E70C853EFE5AFD90130B73F5F1049A38153365</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1002/ajmg.b.30980</idno><idno type="url">https://api.istex.fr/document/68E70C853EFE5AFD90130B73F5F1049A38153365/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001645</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study</title><author><name sortKey="Evangelou, Evangelos" sort="Evangelou, Evangelos" uniqKey="Evangelou E" first="Evangelos" last="Evangelou">Evangelos Evangelou</name><affiliation><mods:affiliation>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Maraganore, Demetrius M" sort="Maraganore, Demetrius M" uniqKey="Maraganore D" first="Demetrius M." last="Maraganore">Demetrius M. Maraganore</name><affiliation><mods:affiliation>Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota</mods:affiliation></affiliation></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><affiliation><mods:affiliation>Institute of Neurological Sciences, National Research Council, Mangone, Italy</mods:affiliation></affiliation></author><author><name sortKey="Brighina, Laura" sort="Brighina, Laura" uniqKey="Brighina L" first="Laura" last="Brighina">Laura Brighina</name><affiliation><mods:affiliation>Section of Neurology, Department of Neuroscience, University of Milano‐Bicocca San Gerardo Hospital, Monza, Italy</mods:affiliation></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name><affiliation><mods:affiliation>INSERM, Unit 708, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UPMC Univ Paris 06, U708, Neuroepidemiology, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name><affiliation><mods:affiliation>Section of Neurology, Department of Neuroscience, University of Milano‐Bicocca San Gerardo Hospital, Monza, Italy</mods:affiliation></affiliation></author><author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name><affiliation><mods:affiliation>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine, Larissa, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute of Biomedical Research & Technology, CERETETH, Larissa, Greece</mods:affiliation></affiliation></author><author><name sortKey="Krueger, Rejko" sort="Krueger, Rejko" uniqKey="Krueger R" first="Rejko" last="Krueger">Rejko Krueger</name><affiliation><mods:affiliation>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Lambert, Jean Harles" sort="Lambert, Jean Harles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name><affiliation><mods:affiliation>INSERM, U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France</mods:affiliation></affiliation></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name><affiliation><mods:affiliation>INSERM, UMR_S679, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Markopoulou, Katerina" sort="Markopoulou, Katerina" uniqKey="Markopoulou K" first="Katerina" last="Markopoulou">Katerina Markopoulou</name><affiliation><mods:affiliation>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine, Larissa, Greece</mods:affiliation></affiliation></author><author><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D." last="Mellick">George D. Mellick</name><affiliation><mods:affiliation>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</mods:affiliation></affiliation></author><author><name sortKey="Meeus, Bram" sort="Meeus, Bram" uniqKey="Meeus B" first="Bram" last="Meeus">Bram Meeus</name><affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>University of Antwerp, Antwerpen, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Pedersen, Nancy L" sort="Pedersen, Nancy L" uniqKey="Pedersen N" first="Nancy L." last="Pedersen">Nancy L. Pedersen</name><affiliation><mods:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name><affiliation><mods:affiliation>Institute of Neurology, University Magna Graecia, Catanzaro, Italy</mods:affiliation></affiliation></author><author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><affiliation><mods:affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</mods:affiliation></affiliation><affiliation><mods:affiliation>University of Antwerp, Antwerpen, Belgium</mods:affiliation></affiliation></author><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><affiliation><mods:affiliation>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name><affiliation><mods:affiliation>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</mods:affiliation></affiliation></author><author><name sortKey="Tan, Eng Ing" sort="Tan, Eng Ing" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name><affiliation><mods:affiliation>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Duke‐NUS Graduate Medical School, Singapore, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><affiliation><mods:affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P. A." last="Ioannidis">John P. A. Ioannidis</name><affiliation><mods:affiliation>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Biomedical Research Institute, Foundation for Research and Technology‐Hellas, Ioannina, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title level="j" type="abbrev">Am. J. Med. Genet.</title><idno type="ISSN">1552-4841</idno><idno type="eISSN">1552-485X</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-01">2010-01</date><biblScope unit="volume">153B</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="220">220</biblScope><biblScope unit="page" to="228">228</biblScope></imprint><idno type="ISSN">1552-4841</idno></series><idno type="istex">68E70C853EFE5AFD90130B73F5F1049A38153365</idno><idno type="DOI">10.1002/ajmg.b.30980</idno><idno type="ArticleID">AJMG30980</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1552-4841</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>genome‐wide association</term><term>meta‐analysis</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta‐analysis of the first two GWA investigations might be replicable in different populations. We examined six single‐nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the “Genetic Epidemiology of Parkinson's Disease” (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98–1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques. © 2009 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Evangelos Evangelou</name><affiliations><json:string>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</json:string><json:string>Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland</json:string></affiliations></json:item><json:item><name>Demetrius M. Maraganore</name><affiliations><json:string>Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota</json:string></affiliations></json:item><json:item><name>Grazia Annesi</name><affiliations><json:string>Institute of Neurological Sciences, National Research Council, Mangone, Italy</json:string></affiliations></json:item><json:item><name>Laura Brighina</name><affiliations><json:string>Section of Neurology, Department of Neuroscience, University of Milano‐Bicocca San Gerardo Hospital, Monza, Italy</json:string></affiliations></json:item><json:item><name>Alexis Brice</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string></affiliations></json:item><json:item><name>Alexis Elbaz</name><affiliations><json:string>INSERM, Unit 708, Paris, France</json:string><json:string>UPMC Univ Paris 06, U708, Neuroepidemiology, Paris, France</json:string></affiliations></json:item><json:item><name>Carlo Ferrarese</name><affiliations><json:string>Section of Neurology, Department of Neuroscience, University of Milano‐Bicocca San Gerardo Hospital, Monza, Italy</json:string></affiliations></json:item><json:item><name>Georgios M. Hadjigeorgiou</name><affiliations><json:string>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine, Larissa, Greece</json:string><json:string>Institute of Biomedical Research & Technology, CERETETH, Larissa, Greece</json:string></affiliations></json:item><json:item><name>Rejko Krueger</name><affiliations><json:string>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</json:string></affiliations></json:item><json:item><name>Jean‐Charles Lambert</name><affiliations><json:string>INSERM, U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France</json:string></affiliations></json:item><json:item><name>Suzanne Lesage</name><affiliations><json:string>INSERM, UMR_S679, Paris, France</json:string></affiliations></json:item><json:item><name>Katerina Markopoulou</name><affiliations><json:string>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine, Larissa, Greece</json:string></affiliations></json:item><json:item><name>George D. Mellick</name><affiliations><json:string>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</json:string></affiliations></json:item><json:item><name>Bram Meeus</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</json:string><json:string>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</json:string><json:string>University of Antwerp, Antwerpen, Belgium</json:string></affiliations></json:item><json:item><name>Nancy L. Pedersen</name><affiliations><json:string>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</json:string></affiliations></json:item><json:item><name>Aldo Quattrone</name><affiliations><json:string>Institute of Neurology, University Magna Graecia, Catanzaro, Italy</json:string></affiliations></json:item><json:item><name>Christine Van Broeckhoven</name><affiliations><json:string>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</json:string><json:string>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</json:string><json:string>University of Antwerp, Antwerpen, Belgium</json:string></affiliations></json:item><json:item><name>Manu Sharma</name><affiliations><json:string>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</json:string></affiliations></json:item><json:item><name>Peter A. Silburn</name><affiliations><json:string>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</json:string></affiliations></json:item><json:item><name>Eng‐King Tan</name><affiliations><json:string>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore, Singapore</json:string><json:string>Duke‐NUS Graduate Medical School, Singapore, Singapore</json:string></affiliations></json:item><json:item><name>Karin Wirdefeldt</name><affiliations><json:string>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</json:string></affiliations></json:item><json:item><name>John P.A. Ioannidis</name><affiliations><json:string>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</json:string><json:string>Biomedical Research Institute, Foundation for Research and Technology‐Hellas, Ioannina, Greece</json:string><json:string>Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts</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>meta‐analysis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>genome‐wide association</value></json:item></subject><articleId><json:string>AJMG30980</json:string></articleId><language><json:string>eng</json:string></language><abstract>Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta‐analysis of the first two GWA investigations might be replicable in different populations. We examined six single‐nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the “Genetic Epidemiology of Parkinson's Disease” (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98–1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques. © 2009 Wiley‐Liss, Inc.</abstract><qualityIndicators><score>7.477</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>3</keywordCount><abstractCharCount>1760</abstractCharCount><pdfWordCount>4477</pdfWordCount><pdfCharCount>33039</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>260</abstractWordCount></qualityIndicators><title>Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study</title><corporate><json:item><name>for the Genetic Epidemiology of Parkinson's Disease (GEOPD) Consortium</name></json:item></corporate><genre><json:string>article</json:string></genre><host><volume>153B</volume><publisherId><json:string>AJMG</json:string></publisherId><pages><total>9</total><last>228</last><first>220</first></pages><issn><json:string>1552-4841</json:string></issn><issue>1</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>1552-485X</json:string></eissn><title>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><doi><json:string>10.1002/(ISSN)1552-485X</json:string></doi></host><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1002/ajmg.b.30980</json:string></doi><id>68E70C853EFE5AFD90130B73F5F1049A38153365</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/68E70C853EFE5AFD90130B73F5F1049A38153365/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/68E70C853EFE5AFD90130B73F5F1049A38153365/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/68E70C853EFE5AFD90130B73F5F1049A38153365/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2010</date></publicationStmt><notesStmt><note type="content">*How to Cite this Article: Evangelou E, Maraganore DM, Annesi G, Brighina L, Brice A, Elbaz A, Ferrarese C, Hadjigeorgiou GM, Krueger R, Lambert J‐C, Lesage S, Markopoulou K, Mellick GD, Meeus B, Pedersen NL, Quattrone A, Van Broeckhoven C, Sharma M, Silburn PA, Tan EK, Wirdefeldt K, Ioannidis JPA. 2010. Non‐Replication of Association for Six Polymorphisms From Meta‐Analysis of Genome‐Wide Association Studies of Parkinson's Disease: Large‐Scale Collaborative Study. Am J Med Genet Part B 153B:220–228.</note><note>Inserm</note><note>MSA</note><note>Agence Nationale de la Recherche, Agence Française de Sécurité Sanitaire de l'Environnement et du Travail, France Parkinson</note><note>FIRB 2003 GENOPOLIS Project - No. RBLA038RMA_003;</note><note>National Institutes of Health (NIH) - No. 2R01 ES10751; No. ES10758; No. AG 08724;</note><note>Michael J. Fox Grants (Linked Efforts to Accelerate Parkinson's Solutions, and Edmond J. Safra Global Genetics Consortia)</note><note>The Swedish Medical Research Council, the Swedish Society of Medicine and the Parkinson Foundation in Sweden</note><note>VIB Genetic Service Facility</note><note>The Biobank of the Institute Born‐Bunge</note><note>Fund for Scientific Research Flanders, the Institute for Science and Technology – Flanders (IWT‐V)</note><note>Foundation for Alzheimer Research (SAO/FRMA)</note><note>Interuniversity Attraction Poles Program P6/43 of the Belgian Science Policy Office, Belgium</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study</title><author><orgName>for the Genetic Epidemiology of Parkinson's Disease (GEOPD) Consortium</orgName></author><author><persName><forename type="first">Evangelos</forename><surname>Evangelou</surname></persName><affiliation>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</affiliation><affiliation>Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland</affiliation></author><author><persName><forename type="first">Demetrius M.</forename><surname>Maraganore</surname></persName><affiliation>Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota</affiliation></author><author><persName><forename type="first">Grazia</forename><surname>Annesi</surname></persName><affiliation>Institute of Neurological Sciences, National Research Council, Mangone, Italy</affiliation></author><author><persName><forename type="first">Laura</forename><surname>Brighina</surname></persName><affiliation>Section of Neurology, Department of Neuroscience, University of Milano‐Bicocca San Gerardo Hospital, Monza, Italy</affiliation></author><author><persName><forename type="first">Alexis</forename><surname>Brice</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation></author><author><persName><forename type="first">Alexis</forename><surname>Elbaz</surname></persName><affiliation>INSERM, Unit 708, Paris, France</affiliation><affiliation>UPMC Univ Paris 06, U708, Neuroepidemiology, Paris, France</affiliation></author><author><persName><forename type="first">Carlo</forename><surname>Ferrarese</surname></persName><affiliation>Section of Neurology, Department of Neuroscience, University of Milano‐Bicocca San Gerardo Hospital, Monza, Italy</affiliation></author><author><persName><forename type="first">Georgios M.</forename><surname>Hadjigeorgiou</surname></persName><affiliation>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine, Larissa, Greece</affiliation><affiliation>Institute of Biomedical Research & Technology, CERETETH, Larissa, Greece</affiliation></author><author><persName><forename type="first">Rejko</forename><surname>Krueger</surname></persName><affiliation>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</affiliation></author><author><persName><forename type="first">Jean‐Charles</forename><surname>Lambert</surname></persName><affiliation>INSERM, U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France</affiliation></author><author><persName><forename type="first">Suzanne</forename><surname>Lesage</surname></persName><affiliation>INSERM, UMR_S679, Paris, France</affiliation></author><author><persName><forename type="first">Katerina</forename><surname>Markopoulou</surname></persName><affiliation>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine, Larissa, Greece</affiliation></author><author><persName><forename type="first">George D.</forename><surname>Mellick</surname></persName><affiliation>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</affiliation></author><author><persName><forename type="first">Bram</forename><surname>Meeus</surname></persName><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</affiliation><affiliation>University of Antwerp, Antwerpen, Belgium</affiliation></author><author><persName><forename type="first">Nancy L.</forename><surname>Pedersen</surname></persName><affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</affiliation></author><author><persName><forename type="first">Aldo</forename><surname>Quattrone</surname></persName><affiliation>Institute of Neurology, University Magna Graecia, Catanzaro, Italy</affiliation></author><author><persName><forename type="first">Christine</forename><surname>Van Broeckhoven</surname></persName><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</affiliation><affiliation>University of Antwerp, Antwerpen, Belgium</affiliation></author><author><persName><forename type="first">Manu</forename><surname>Sharma</surname></persName><affiliation>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</affiliation></author><author><persName><forename type="first">Peter A.</forename><surname>Silburn</surname></persName><affiliation>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</affiliation></author><author><persName><forename type="first">Eng‐King</forename><surname>Tan</surname></persName><affiliation>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore, Singapore</affiliation><affiliation>Duke‐NUS Graduate Medical School, Singapore, Singapore</affiliation></author><author><persName><forename type="first">Karin</forename><surname>Wirdefeldt</surname></persName><affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</affiliation></author><author><persName><forename type="first">John P.A.</forename><surname>Ioannidis</surname></persName><note type="correspondence"><p>Correspondence: Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.</p></note><affiliation>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</affiliation><affiliation>Biomedical 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J. Med. Genet.</title><idno type="pISSN">1552-4841</idno><idno type="eISSN">1552-485X</idno><idno type="DOI">10.1002/(ISSN)1552-485X</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-01"></date><biblScope unit="volume">153B</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="220">220</biblScope><biblScope unit="page" to="228">228</biblScope></imprint></monogr><idno type="istex">68E70C853EFE5AFD90130B73F5F1049A38153365</idno><idno type="DOI">10.1002/ajmg.b.30980</idno><idno type="ArticleID">AJMG30980</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta‐analysis of the first two GWA investigations might be replicable in different populations. We examined six single‐nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the “Genetic Epidemiology of Parkinson's Disease” (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98–1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques. © 2009 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>meta‐analysis</term></item><item><term>genome‐wide association</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="2008-11-27">Received</change><change when="2009-04-10">Registration</change><change when="2010-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/68E70C853EFE5AFD90130B73F5F1049A38153365/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)1552-485X</doi><issn type="print">1552-4841</issn><issn type="electronic">1552-485X</issn><idGroup><id type="product" value="AJMG"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="AMERICAN JOURNAL OF MEDICAL GENETICS PART B: NEUROPSYCHIATRIC GENETICS">American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title><title type="short">Am. 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countryCode="DE" type="organization"><unparsedAffiliation>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af12" countryCode="FR" type="organization"><unparsedAffiliation>INSERM, U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France</unparsedAffiliation></affiliation><affiliation xml:id="af13" countryCode="AU" type="organization"><unparsedAffiliation>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</unparsedAffiliation></affiliation><affiliation xml:id="af14" countryCode="BE" type="organization"><unparsedAffiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</unparsedAffiliation></affiliation><affiliation xml:id="af15" countryCode="BE" type="organization"><unparsedAffiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</unparsedAffiliation></affiliation><affiliation xml:id="af16" countryCode="BE" type="organization"><unparsedAffiliation>University of Antwerp, Antwerpen, Belgium</unparsedAffiliation></affiliation><affiliation xml:id="af17" countryCode="SE" type="organization"><unparsedAffiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</unparsedAffiliation></affiliation><affiliation xml:id="af18" countryCode="IT" type="organization"><unparsedAffiliation>Institute of Neurology, University Magna Graecia, Catanzaro, Italy</unparsedAffiliation></affiliation><affiliation xml:id="af19" countryCode="SG" type="organization"><unparsedAffiliation>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore, Singapore</unparsedAffiliation></affiliation><affiliation xml:id="af20" countryCode="SG" type="organization"><unparsedAffiliation>Duke‐NUS Graduate Medical School, Singapore, Singapore</unparsedAffiliation></affiliation><affiliation xml:id="af21" countryCode="GR" type="organization"><unparsedAffiliation>Biomedical Research Institute, Foundation for Research and Technology‐Hellas, Ioannina, Greece</unparsedAffiliation></affiliation><affiliation xml:id="af22" countryCode="US" type="organization"><unparsedAffiliation>Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">meta‐analysis</keyword><keyword xml:id="kwd3">genome‐wide association</keyword></keywordGroup><fundingInfo><fundingAgency>Inserm</fundingAgency></fundingInfo><fundingInfo><fundingAgency>MSA</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Agence Nationale de la Recherche, Agence Française de Sécurité Sanitaire de l'Environnement et du Travail, France Parkinson</fundingAgency></fundingInfo><fundingInfo><fundingAgency>FIRB 2003 GENOPOLIS Project</fundingAgency><fundingNumber>RBLA038RMA_003</fundingNumber></fundingInfo><fundingInfo><fundingAgency>National Institutes of Health (NIH)</fundingAgency><fundingNumber>2R01 ES10751</fundingNumber><fundingNumber>ES10758</fundingNumber><fundingNumber>AG 08724</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Michael J. Fox Grants (Linked Efforts to Accelerate Parkinson's Solutions, and Edmond J. Safra Global Genetics Consortia)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>The Swedish Medical Research Council, the Swedish Society of Medicine and the Parkinson Foundation in Sweden</fundingAgency></fundingInfo><fundingInfo><fundingAgency>VIB Genetic Service Facility</fundingAgency></fundingInfo><fundingInfo><fundingAgency>The Biobank of the Institute Born‐Bunge</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Fund for Scientific Research Flanders, the Institute for Science and Technology – Flanders (IWT‐V)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Foundation for Alzheimer Research (SAO/FRMA)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Interuniversity Attraction Poles Program P6/43 of the Belgian Science Policy Office, Belgium</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta‐analysis of the first two GWA investigations might be replicable in different populations. We examined six single‐nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the “Genetic Epidemiology of Parkinson's Disease” (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98–1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques. © 2009 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>How to Cite this Article: Evangelou E, Maraganore DM, Annesi G, Brighina L, Brice A, Elbaz A, Ferrarese C, Hadjigeorgiou GM, Krueger R, Lambert J‐C, Lesage S, Markopoulou K, Mellick GD, Meeus B, Pedersen NL, Quattrone A, Van Broeckhoven C, Sharma M, Silburn PA, Tan EK, Wirdefeldt K, Ioannidis JPA. 2010. Non‐Replication of Association for Six Polymorphisms From Meta‐Analysis of Genome‐Wide Association Studies of Parkinson's Disease: Large‐Scale Collaborative Study. Am J Med Genet Part B 153B:220–228.</p></note><note xml:id="fn2"><p><i>Australia</i>: G.T. Sutherland (Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD), G.A. Siebert (Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD). <i>Belgium</i>: Jessie Theuns, PhD (Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB; Laboratory of Neurogenetics, Institute Born‐Bunge; University of Antwerp, Antwerpen), David Crosiers (Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB; Laboratory of Neurobiology, Institute Born‐Bunge; University of Antwerp and University Hospital Antwerp, Antwerpen), Barbara Pickut, MD (Memory Clinic and Division of Neurology, ZNA Middelheim, Antwerpen), Philippe Pals, MD, PhD (Laboratory of Neurobiology, Institute Born‐Bunge and University Hospital Antwerp; Antwerpen), Sebastiaan Engelborghs, MD, PhD (Laboratory of Neurochemistry and Behavior, Institute Born‐Bunge; University of Antwerp and Memory Clinic and Division of Neurology, ZNA Middelheim, Antwerpen Belgium), Karen Nuytemans (Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB; Laboratory of Neurogenetics, Institute Born‐Bunge; and University of Antwerp, Antwerpen), Peter P. De Deyn, MD, PhD (Laboratory of Neurochemistry and Behavior, Institute Born‐Bunge; University of Antwerp; and Memory Clinic and Division of Neurology, ZNA Middelheim, Antwerpen), Patrick Cras, MD, PhD (Laboratory of Neurobiology, Institute Born‐Bunge; University of Antwerp; and University Hospital Antwerp, Antwerpen). <i>France</i>: From the French Parkinson's Disease Genetics Study Group: Agid Y, Bonnet A‐M, Borg M, Brice A, Broussolle E, Damier P, Destée A, Dürr A, Durif F, Lesage S, Lohmann E, Pollak P, Rascol O, Tison F, Tranchant C, Viallet F, Vidailhet M. Also, Christophe Tzourio (Inserm U708, Paris), Philippe Amouyel (Inserm U744, Lille), Marie‐Anne Loriot (Inserm UMRS775, Paris). <i>Germany</i>: Prof. Thomas Gasser (Department of Neurology, University Hospital Tuebingen), Olaf Riess, PhD (Department of Neurology, University Hospital Tuebingen), Daniela Berg, MD (Department of Neurology, University Hospital Tuebingen), Claudia Schulte, MSc (Department of Neurology, University Hospital Tuebingen). Also, Christine Klein, PhD (Department of Neurology, University of Lübeck), Ana Djarmati, PhD (Department of Neurology, University of Lübeck), Katja Lohmann, PhD (Department of Neurology, University of Lübeck). <i>Greece</i>: Georgia Xiromerisiou, MD (Institute of Biomedical Research & Technology, CERETETH, Larissa), Efthimios Dardiotis, MD (Faculty of Medicine, Department of Neurology, University of Thessaly; and Institute of Biomedical Research & Technology, CERETETH, Larissa), Persa Kountra, MD (Faculty of Medicine, Department of Neurology, University of Thessaly). <i>Japan</i>: Nobutaka Hattori, MD, PhD (Department of Neurology, Juntendo University School of Medicine, Tokyo), Hiroyuki Tomiyama, MD, PhD (Department of Neurology, Juntendo University School of Medicine, Tokyo), Manabu Funayama, PhD (Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Tokyo), Hiroyo Yoshino, BS (Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Tokyo), Yuanzhe Li, MD, PhD (Department of Neurology, Juntendo University School of Medicine, Tokyo). <i>Italy</i>: Enza Maria Valente, MD, PhD (Mendel Institute, Casa Sollievo della Sofferenza Hospital, Rome), Alessandro Ferraris, MD, (Mendel Institute, Casa Sollievo della Sofferenza Hospital, Rome), Anna Rita Bentivoglio, MD, PhD (Institute of Neurology, Catholic University, Rome), Tamara Ialongo, MD, PhD (Institute of Neurology, Catholic University, Rome), Chiara Riva, PhD (Department of Neuroscience, University of Milano‐Bicocca, Monza), Barbara Corradi, PhD (Department of Paediatrics, University of Milano‐Bicocca, Monza). <i>Poland</i>: Grzegorz Opala, MD, PhD (Department of Neurology, Aging, Degenerative and Cerebrovascular Disorders, Medical University of Silesia, Katowice), Barbara Jasinska‐Myga, MD, PhD (Department of Neurology, Aging, Degenerative and Cerebrovascular Disorders, Medical University of Silesia, Katowice), Gabriela Klodowska‐Duda, MD, PhD (Department of Neurology, Aging, Degenerative and Cerebrovascular Disorders, Medical University of Silesia, Katowice), Magdalena Boczarska‐Jedynak, MD, PhD (Department of Neurology, Aging, Degenerative and Cerebrovascular Disorders, Medical University of Silesia, Katowice). <i>Sweden</i>: Andrea Carmine Belin, PhD (Department of Neuroscience, Karolinska Institutet, Stockholm), Prof. Lars Olson (Department of Neuroscience, Karolinska Institutet, Stockholm), Dagmar Galter, PhD (Department of Neuroscience, Karolinska Institutet, Stockholm), Marie Westerlund, PhD (Department of Neuroscience, Karolinska Institutet, Stockholm), Olof Sydow, PhD (Department of Clinical Neuroscience, Karolinska University Hospital, Stockholm). Also Christer Nilsson, MD, PhD (Department of Geriatric Psychiatry, Lund University), Andreas Puschmann, MD (Department of Neurology, Lund University Hospital, Department of Geriatric Psychiatry, Lund University). <i>USA</i>: Demetrius M. Maraganore, MD (Department of Neurology, Mayo Clinic, Rochester, MN), J. Eric Ahlskog PhD, MD (Department of Neurology, Mayo Clinic, Rochester, MN, USA), Mariza de Andrade, PhD (Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA), Timothy G. Lesnick, MS (Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA), and Walter A. Rocca, MD, MPH (Departments of Neurology and Health Sciences Research, Mayo Clinic, Rochester, MN, USA). Also, Harvey Checkoway, PhD (Department of Environmental and Occupational Health Sciences, University of Washington).</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study</title></titleInfo><name type="personal"><namePart type="given">Evangelos</namePart><namePart type="family">Evangelou</namePart><affiliation>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</affiliation><affiliation>Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Demetrius M.</namePart><namePart type="family">Maraganore</namePart><affiliation>Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Grazia</namePart><namePart type="family">Annesi</namePart><affiliation>Institute of Neurological Sciences, National Research Council, Mangone, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Laura</namePart><namePart type="family">Brighina</namePart><affiliation>Section of Neurology, Department of Neuroscience, University of Milano‐Bicocca San Gerardo Hospital, Monza, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alexis</namePart><namePart type="family">Brice</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alexis</namePart><namePart type="family">Elbaz</namePart><affiliation>INSERM, Unit 708, Paris, France</affiliation><affiliation>UPMC Univ Paris 06, U708, Neuroepidemiology, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Carlo</namePart><namePart type="family">Ferrarese</namePart><affiliation>Section of Neurology, Department of Neuroscience, University of Milano‐Bicocca San Gerardo Hospital, Monza, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Georgios M.</namePart><namePart type="family">Hadjigeorgiou</namePart><affiliation>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine, Larissa, Greece</affiliation><affiliation>Institute of Biomedical Research & Technology, CERETETH, Larissa, Greece</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rejko</namePart><namePart type="family">Krueger</namePart><affiliation>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean‐Charles</namePart><namePart type="family">Lambert</namePart><affiliation>INSERM, U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Suzanne</namePart><namePart type="family">Lesage</namePart><affiliation>INSERM, UMR_S679, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Katerina</namePart><namePart type="family">Markopoulou</namePart><affiliation>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine, Larissa, Greece</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">George D.</namePart><namePart type="family">Mellick</namePart><affiliation>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bram</namePart><namePart type="family">Meeus</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</affiliation><affiliation>University of Antwerp, Antwerpen, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nancy L.</namePart><namePart type="family">Pedersen</namePart><affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Aldo</namePart><namePart type="family">Quattrone</namePart><affiliation>Institute of Neurology, University Magna Graecia, Catanzaro, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine</namePart><namePart type="family">Van Broeckhoven</namePart><affiliation>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium</affiliation><affiliation>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, Belgium</affiliation><affiliation>University of Antwerp, Antwerpen, Belgium</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Manu</namePart><namePart type="family">Sharma</namePart><affiliation>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter A.</namePart><namePart type="family">Silburn</namePart><affiliation>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eng‐King</namePart><namePart type="family">Tan</namePart><affiliation>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore, Singapore</affiliation><affiliation>Duke‐NUS Graduate Medical School, Singapore, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karin</namePart><namePart type="family">Wirdefeldt</namePart><affiliation>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John P.A.</namePart><namePart type="family">Ioannidis</namePart><affiliation>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece</affiliation><affiliation>Biomedical Research Institute, Foundation for Research and Technology‐Hellas, Ioannina, Greece</affiliation><affiliation>Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts</affiliation><description>Correspondence: Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="corporate"><namePart>for the Genetic Epidemiology of Parkinson's Disease (GEOPD) Consortium</namePart><description>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, GreeceInstitute of Microbiology, University Hospital and University of Lausanne, Lausanne, SwitzerlandDepartment of Neurology, Mayo Clinic College of Medicine, Rochester, MinnesotaInstitute of Neurological Sciences, National Research Council, Mangone, ItalySection of Neurology, Department of Neuroscience, University of Milano‐Bicocca San Gerardo Hospital, Monza, ItalyINSERM, UMR_S679, Paris, FranceINSERM, Unit 708, Paris, FranceUPMC Univ Paris 06, U708, Neuroepidemiology, Paris, FranceDepartment of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine, Larissa, GreeceInstitute of Biomedical Research & Technology, CERETETH, Larissa, GreeceDepartment of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen, GermanyINSERM, U744, Institut Pasteur de Lille, Université de Lille 2, Lille, FranceEskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD, AustraliaNeurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, BelgiumLaboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen, BelgiumUniversity of Antwerp, Antwerpen, BelgiumDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenInstitute of Neurology, University Magna Graecia, Catanzaro, ItalyDepartment of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore, SingaporeDuke‐NUS Graduate Medical School, Singapore, SingaporeBiomedical Research Institute, Foundation for Research and Technology‐Hellas, Ioannina, GreeceInstitute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts</description></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">2010-01</dateIssued><dateCaptured encoding="w3cdtf">2008-11-27</dateCaptured><dateValid encoding="w3cdtf">2009-04-10</dateValid><copyrightDate encoding="w3cdtf">2010</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="figures">1</extent><extent unit="tables">3</extent><extent unit="references">24</extent><extent unit="words">6312</extent></physicalDescription><abstract lang="en">Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta‐analysis of the first two GWA investigations might be replicable in different populations. We examined six single‐nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the “Genetic Epidemiology of Parkinson's Disease” (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98–1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques. © 2009 Wiley‐Liss, Inc.</abstract><note type="content">*How to Cite this Article: Evangelou E, Maraganore DM, Annesi G, Brighina L, Brice A, Elbaz A, Ferrarese C, Hadjigeorgiou GM, Krueger R, Lambert J‐C, Lesage S, Markopoulou K, Mellick GD, Meeus B, Pedersen NL, Quattrone A, Van Broeckhoven C, Sharma M, Silburn PA, Tan EK, Wirdefeldt K, Ioannidis JPA. 2010. Non‐Replication of Association for Six Polymorphisms From Meta‐Analysis of Genome‐Wide Association Studies of Parkinson's Disease: Large‐Scale Collaborative Study. Am J Med Genet Part B 153B:220–228.</note><note type="funding">Inserm</note><note type="funding">MSA</note><note type="funding">Agence Nationale de la Recherche, Agence Française de Sécurité Sanitaire de l'Environnement et du Travail, France Parkinson</note><note type="funding">FIRB 2003 GENOPOLIS Project - No. RBLA038RMA_003; </note><note type="funding">National Institutes of Health (NIH) - No. 2R01 ES10751; No. ES10758; No. AG 08724; </note><note type="funding">Michael J. Fox Grants (Linked Efforts to Accelerate Parkinson's Solutions, and Edmond J. Safra Global Genetics Consortia)</note><note type="funding">The Swedish Medical Research Council, the Swedish Society of Medicine and the Parkinson Foundation in Sweden</note><note type="funding">VIB Genetic Service Facility</note><note type="funding">The Biobank of the Institute Born‐Bunge</note><note type="funding">Fund for Scientific Research Flanders, the Institute for Science and Technology – Flanders (IWT‐V)</note><note type="funding">Foundation for Alzheimer Research (SAO/FRMA)</note><note type="funding">Interuniversity Attraction Poles Program P6/43 of the Belgian Science Policy Office, Belgium</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>meta‐analysis</topic><topic>genome‐wide association</topic></subject><relatedItem type="host"><titleInfo><title>American Journal of Medical Genetics Part B: Neuropsychiatric Genetics</title></titleInfo><titleInfo type="abbreviated"><title>Am. J. Med. Genet.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">1552-4841</identifier><identifier type="eISSN">1552-485X</identifier><identifier type="DOI">10.1002/(ISSN)1552-485X</identifier><identifier type="PublisherID">AJMG</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>153B</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>220</start><end>228</end><total>9</total></extent></part></relatedItem><relatedItem type="preceding"><titleInfo><title>American Journal of Medical Genetics</title></titleInfo><identifier type="ISSN">0148-7299</identifier><identifier type="ISSN">1096-8628</identifier><part><date point="end">2004</date></part></relatedItem><identifier type="istex">68E70C853EFE5AFD90130B73F5F1049A38153365</identifier><identifier type="DOI">10.1002/ajmg.b.30980</identifier><identifier type="ArticleID">AJMG30980</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2009 Wiley‐Liss, Inc.</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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