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 : 007C72 ( Main/Merge ); précédent : 007C71; suivant : 007C73Non-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 [Grèce, Suisse] ; Demetrius M. Maraganore [États-Unis] ; Grazia Annesi [Italie] ; Laura Brighina [Italie] ; Alexis Brice [France] ; Alexis Elbaz [France] ; Carlo Ferrarese [Italie] ; Georgios M. Hadjigeorgiou [Grèce] ; Rejko Krueger [Grèce] ; Jean-Charles Lambert [France] ; Suzanne Lesage [France] ; Katerina Markopoulou [Grèce] ; George D. Mellick [Australie] ; Bram Meeus [Belgique] ; Nancy L. Pedersen [Suède] ; Aldo Quattrone [Italie] ; Christine Van Broeckhoven [Belgique] ; Manu Sharma [Allemagne] ; Peter A. Silburn [Australie] ; Eng-King Tan [Singapour] ; Karin Wirdefeldt [Suède] ; John P. A. Ioannidis [Grèce]Source :
- American journal of medical genetics. Part B, Neuropsychiatric genetics [ 1552-4841 ] ; 2010.
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- topic : Association.
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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.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">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 wicri:level="1"><inist:fA14 i1="01"><s1>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of loannina Medical School</s1><s2>loannina</s2><s3>GRC</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>loannina</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Microbiology, University Hospital and University of Lausanne</s1><s2>Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ></inist:fA14><country>Suisse</country><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></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 wicri:level="2"><inist:fA14 i1="03"><s1>Department of Neurology, Mayo Clinic College of Medicine</s1><s2>Rochester, Minnesota</s2><s3>USA</s3><sZ>2 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institute of Neurological Sciences, National Research Council</s1><s2>Mangone</s2><s3>ITA</s3><sZ>3 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Mangone</wicri:noRegion></affiliation></author><author><name sortKey="Brighina, Laura" sort="Brighina, Laura" uniqKey="Brighina L" first="Laura" last="Brighina">Laura Brighina</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Section of Neurology, Department of Neuroscience, University of Milano-Bicocca San Gerardo Hospital</s1><s2>Monza</s2><s3>ITA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Monza</wicri:noRegion></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM, UMR_S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>5 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>INSERM, Unit 708</s1><s2>Paris</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>UPMC Univ Paris 06, U708, Neuroepidemiology</s1><s2>Paris</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Section of Neurology, Department of Neuroscience, University of Milano-Bicocca San Gerardo Hospital</s1><s2>Monza</s2><s3>ITA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Monza</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="09"><s1>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine</s1><s2>Larissa</s2><s3>GRC</s3><sZ>8 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>Larissa</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Institute of Biomedical Research & Technology, CERETETH</s1><s2>Larissa</s2><s3>GRC</s3><sZ>8 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>Larissa</wicri:noRegion></affiliation></author><author><name sortKey="Krueger, Rejko" sort="Krueger, Rejko" uniqKey="Krueger R" first="Rejko" last="Krueger">Rejko Krueger</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of loannina Medical School</s1><s2>loannina</s2><s3>GRC</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>loannina</wicri:noRegion></affiliation></author><author><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>INSERM, U744, Institut Pasteur de Lille, Université de Lille 2</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM, UMR_S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>5 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Markopoulou, Katerina" sort="Markopoulou, Katerina" uniqKey="Markopoulou K" first="Katerina" last="Markopoulou">Katerina Markopoulou</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine</s1><s2>Larissa</s2><s3>GRC</s3><sZ>8 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>Larissa</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="13"><s1>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University</s1><s2>Nathan, QLD</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Nathan, QLD</wicri:noRegion></affiliation></author><author><name sortKey="Meeus, Bram" sort="Meeus, Bram" uniqKey="Meeus B" first="Bram" last="Meeus">Bram Meeus</name><affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Laboratory of Neurogenetics, Institute Born-Bunge</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>University of Antwerp</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><placeName><settlement type="city">Anvers</settlement><region>Région flamande</region><region type="district" nuts="2">Province d'Anvers</region></placeName><orgName type="university">Université d'Anvers</orgName></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 wicri:level="3"><inist:fA14 i1="17"><s1>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>15 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Institute of Neurology, University Magna Graecia</s1><s2>Catanzaro</s2><s3>ITA</s3><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Catanzaro</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="14"><s1>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Laboratory of Neurogenetics, Institute Born-Bunge</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>University of Antwerp</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><placeName><settlement type="city">Anvers</settlement><region>Région flamande</region><region type="district" nuts="2">Province d'Anvers</region></placeName><orgName type="university">Université d'Anvers</orgName></affiliation></author><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen</s1><s2>Tuebingen</s2><s3>DEU</s3><sZ>18 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></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 wicri:level="1"><inist:fA14 i1="13"><s1>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University</s1><s2>Nathan, QLD</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Nathan, QLD</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name><affiliation wicri:level="1"><inist:fA14 i1="19"><s1>Department of Neurology, Singapore General Hospital, National Neuroscience Institute</s1><s2>Singapore</s2><s3>SGP</s3><sZ>20 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Singapore</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Duke-NUS Graduate Medical School</s1><s2>Singapore</s2><s3>SGP</s3><sZ>20 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Duke-NUS Graduate Medical School</wicri:noRegion></affiliation></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><affiliation wicri:level="3"><inist:fA14 i1="17"><s1>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>15 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></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 wicri:level="1"><inist:fA14 i1="01"><s1>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of loannina Medical School</s1><s2>loannina</s2><s3>GRC</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>loannina</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0062774</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0062774 INIST</idno><idno type="RBID">Pascal:10-0062774</idno><idno type="wicri:Area/PascalFrancis/Corpus">002914</idno><idno type="wicri:Area/PascalFrancis/Curation">003670</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">002204</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">002204</idno><idno type="wicri:doubleKey">1552-4841:2010:Evangelou E:non:replication:of</idno><idno type="wicri:Area/Main/Merge">007C72</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">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 wicri:level="1"><inist:fA14 i1="01"><s1>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of loannina Medical School</s1><s2>loannina</s2><s3>GRC</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>loannina</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Institute of Microbiology, University Hospital and University of Lausanne</s1><s2>Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ></inist:fA14><country>Suisse</country><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></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 wicri:level="2"><inist:fA14 i1="03"><s1>Department of Neurology, Mayo Clinic College of Medicine</s1><s2>Rochester, Minnesota</s2><s3>USA</s3><sZ>2 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institute of Neurological Sciences, National Research Council</s1><s2>Mangone</s2><s3>ITA</s3><sZ>3 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Mangone</wicri:noRegion></affiliation></author><author><name sortKey="Brighina, Laura" sort="Brighina, Laura" uniqKey="Brighina L" first="Laura" last="Brighina">Laura Brighina</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Section of Neurology, Department of Neuroscience, University of Milano-Bicocca San Gerardo Hospital</s1><s2>Monza</s2><s3>ITA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Monza</wicri:noRegion></affiliation></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM, UMR_S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>5 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>INSERM, Unit 708</s1><s2>Paris</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>UPMC Univ Paris 06, U708, Neuroepidemiology</s1><s2>Paris</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Section of Neurology, Department of Neuroscience, University of Milano-Bicocca San Gerardo Hospital</s1><s2>Monza</s2><s3>ITA</s3><sZ>4 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Monza</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="09"><s1>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine</s1><s2>Larissa</s2><s3>GRC</s3><sZ>8 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>Larissa</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Institute of Biomedical Research & Technology, CERETETH</s1><s2>Larissa</s2><s3>GRC</s3><sZ>8 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>Larissa</wicri:noRegion></affiliation></author><author><name sortKey="Krueger, Rejko" sort="Krueger, Rejko" uniqKey="Krueger R" first="Rejko" last="Krueger">Rejko Krueger</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of loannina Medical School</s1><s2>loannina</s2><s3>GRC</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>loannina</wicri:noRegion></affiliation></author><author><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name><affiliation wicri:level="3"><inist:fA14 i1="12"><s1>INSERM, U744, Institut Pasteur de Lille, Université de Lille 2</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM, UMR_S679</s1><s2>Paris</s2><s3>FRA</s3><sZ>5 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Markopoulou, Katerina" sort="Markopoulou, Katerina" uniqKey="Markopoulou K" first="Katerina" last="Markopoulou">Katerina Markopoulou</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, School of Medicine</s1><s2>Larissa</s2><s3>GRC</s3><sZ>8 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>Larissa</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="13"><s1>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University</s1><s2>Nathan, QLD</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Nathan, QLD</wicri:noRegion></affiliation></author><author><name sortKey="Meeus, Bram" sort="Meeus, Bram" uniqKey="Meeus B" first="Bram" last="Meeus">Bram Meeus</name><affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Laboratory of Neurogenetics, Institute Born-Bunge</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>University of Antwerp</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><placeName><settlement type="city">Anvers</settlement><region>Région flamande</region><region type="district" nuts="2">Province d'Anvers</region></placeName><orgName type="university">Université d'Anvers</orgName></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 wicri:level="3"><inist:fA14 i1="17"><s1>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>15 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Institute of Neurology, University Magna Graecia</s1><s2>Catanzaro</s2><s3>ITA</s3><sZ>16 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Catanzaro</wicri:noRegion></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 wicri:level="1"><inist:fA14 i1="14"><s1>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Laboratory of Neurogenetics, Institute Born-Bunge</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>University of Antwerp</s1><s2>Antwerpen</s2><s3>BEL</s3><sZ>14 aut.</sZ><sZ>17 aut.</sZ></inist:fA14><country>Belgique</country><placeName><settlement type="city">Anvers</settlement><region>Région flamande</region><region type="district" nuts="2">Province d'Anvers</region></placeName><orgName type="university">Université d'Anvers</orgName></affiliation></author><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><affiliation wicri:level="3"><inist:fA14 i1="11"><s1>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen</s1><s2>Tuebingen</s2><s3>DEU</s3><sZ>18 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></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 wicri:level="1"><inist:fA14 i1="13"><s1>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University</s1><s2>Nathan, QLD</s2><s3>AUS</s3><sZ>13 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Nathan, QLD</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name><affiliation wicri:level="1"><inist:fA14 i1="19"><s1>Department of Neurology, Singapore General Hospital, National Neuroscience Institute</s1><s2>Singapore</s2><s3>SGP</s3><sZ>20 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Singapore</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Duke-NUS Graduate Medical School</s1><s2>Singapore</s2><s3>SGP</s3><sZ>20 aut.</sZ></inist:fA14><country>Singapour</country><wicri:noRegion>Duke-NUS Graduate Medical School</wicri:noRegion></affiliation></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><affiliation wicri:level="3"><inist:fA14 i1="17"><s1>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet</s1><s2>Stockholm</s2><s3>SWE</s3><sZ>15 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Suède</country><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></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 wicri:level="1"><inist:fA14 i1="01"><s1>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of loannina Medical School</s1><s2>loannina</s2><s3>GRC</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>Grèce</country><wicri:noRegion>loannina</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">American journal of medical genetics. Part B, Neuropsychiatric genetics</title><title level="j" type="abbreviated">Am. j. med. genet., Part B Neuropsychiatr. genet.</title><idno type="ISSN">1552-4841</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">American journal of medical genetics. Part B, Neuropsychiatric genetics</title><title level="j" type="abbreviated">Am. j. med. genet., Part B Neuropsychiatr. genet.</title><idno type="ISSN">1552-4841</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Association</term><term>Evaluation scale</term><term>Genome</term><term>Metaanalysis</term><term>Parkinson disease</term><term>Polymorphism</term><term>Replication</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Réplication</term><term>Association</term><term>Polymorphisme</term><term>Métaanalyse</term><term>Génome</term><term>Echelle d'évaluation</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Association</term></keywords></textClass></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.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Belgique</li><li>France</li><li>Grèce</li><li>Italie</li><li>Singapour</li><li>Suisse</li><li>Suède</li><li>États-Unis</li></country><region><li>Bade-Wurtemberg</li><li>Canton de Vaud</li><li>District de Tübingen</li><li>Hauts-de-France</li><li>Minnesota</li><li>Nord-Pas-de-Calais</li><li>Province d'Anvers</li><li>Région flamande</li><li>Svealand</li><li>Île-de-France</li></region><settlement><li>Anvers</li><li>Lausanne</li><li>Lille</li><li>Paris</li><li>Stockholm</li><li>Tübingen</li></settlement><orgName><li>Université d'Anvers</li></orgName></list><tree><country name="Grèce"><noRegion><name sortKey="Evangelou, Evangelos" sort="Evangelou, Evangelos" uniqKey="Evangelou E" first="Evangelos" last="Evangelou">Evangelos Evangelou</name></noRegion><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name><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><name sortKey="Krueger, Rejko" sort="Krueger, Rejko" uniqKey="Krueger R" first="Rejko" last="Krueger">Rejko Krueger</name><name sortKey="Markopoulou, Katerina" sort="Markopoulou, Katerina" uniqKey="Markopoulou K" first="Katerina" last="Markopoulou">Katerina Markopoulou</name></country><country name="Suisse"><region name="Canton de Vaud"><name sortKey="Evangelou, Evangelos" sort="Evangelou, Evangelos" uniqKey="Evangelou E" first="Evangelos" last="Evangelou">Evangelos Evangelou</name></region></country><country name="États-Unis"><region name="Minnesota"><name sortKey="Maraganore, Demetrius M" sort="Maraganore, Demetrius M" uniqKey="Maraganore D" first="Demetrius M." last="Maraganore">Demetrius M. Maraganore</name></region></country><country name="Italie"><noRegion><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name></noRegion><name sortKey="Brighina, Laura" sort="Brighina, Laura" uniqKey="Brighina L" first="Laura" last="Brighina">Laura Brighina</name><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name></country><country name="France"><region name="Île-de-France"><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></region><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name></country><country name="Australie"><noRegion><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D." last="Mellick">George D. Mellick</name></noRegion><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name></country><country name="Belgique"><noRegion><name sortKey="Meeus, Bram" sort="Meeus, Bram" uniqKey="Meeus B" first="Bram" last="Meeus">Bram Meeus</name></noRegion><name sortKey="Meeus, Bram" sort="Meeus, Bram" uniqKey="Meeus B" first="Bram" last="Meeus">Bram Meeus</name><name sortKey="Meeus, Bram" sort="Meeus, Bram" uniqKey="Meeus B" first="Bram" last="Meeus">Bram Meeus</name><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name></country><country name="Suède"><region name="Svealand"><name sortKey="Pedersen, Nancy L" sort="Pedersen, Nancy L" uniqKey="Pedersen N" first="Nancy L." last="Pedersen">Nancy L. Pedersen</name></region><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name></region></country><country name="Singapour"><noRegion><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name></noRegion><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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