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 : 000049 ( France/Analysis ); précédent : 000048; suivant : 000050Non‐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 [Allemagne] ; 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, États-Unis]Source :
- 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.
Url:
DOI: 10.1002/ajmg.b.30980
Affiliations:
- Allemagne, Australie, Belgique, France, Grèce, Italie, Singapour, Suisse, Suède, États-Unis
- Bade-Wurtemberg, Canton de Vaud, District de Tübingen, Massachusetts, Minnesota, Province d'Anvers, Svealand
- Anvers, Lausanne, Lille, Paris, Stockholm, Tübingen
- Université d'Anvers
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ISTEX:68E70C853EFE5AFD90130B73F5F1049A38153365Le document en format XML
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Mellick</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD</wicri:regionArea><wicri:noRegion>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"><country xml:lang="fr">Belgique</country><wicri:regionArea>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen</wicri:regionArea><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen</wicri:regionArea><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Belgique</country><wicri:regionArea>University of Antwerp, Antwerpen</wicri:regionArea><orgName type="university">Université d'Anvers</orgName><placeName><settlement type="city">Anvers</settlement><region type="district" nuts="2">Province d'Anvers</region></placeName></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"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm</wicri:regionArea><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"><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Neurology, University Magna Graecia, Catanzaro</wicri:regionArea><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"><country xml:lang="fr">Belgique</country><wicri:regionArea>Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen</wicri:regionArea><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>Laboratory of Neurogenetics, Institute Born‐Bunge, Antwerpen</wicri:regionArea><wicri:noRegion>Antwerpen</wicri:noRegion></affiliation><affiliation wicri:level="4"><country xml:lang="fr">Belgique</country><wicri:regionArea>University of Antwerp, Antwerpen</wicri:regionArea><orgName type="university">Université d'Anvers</orgName><placeName><settlement type="city">Anvers</settlement><region type="district" nuts="2">Province d'Anvers</region></placeName></affiliation></author><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Tuebingen</wicri:regionArea><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"><country xml:lang="fr">Australie</country><wicri:regionArea>Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular & Physical Sciences, Griffith University, Nathan, QLD</wicri:regionArea><wicri:noRegion>QLD</wicri:noRegion></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 wicri:level="1"><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore</wicri:regionArea><wicri:noRegion>Singapore</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke‐NUS Graduate Medical School, Singapore</wicri:regionArea><wicri:noRegion>Singapore</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"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm</wicri:regionArea><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"><country xml:lang="fr">Grèce</country><wicri:regionArea>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina</wicri:regionArea><wicri:noRegion>Ioannina</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Biomedical Research Institute, Foundation for Research and Technology‐Hellas, Ioannina</wicri:regionArea><wicri:noRegion>Ioannina</wicri:noRegion></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston</wicri:cityArea></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><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>Massachusetts</li><li>Minnesota</li><li>Province d'Anvers</li><li>Svealand</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="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="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><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></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"><noRegion><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></noRegion><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 Harles" sort="Lambert, Jean Harles" 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="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Krueger, Rejko" sort="Krueger, Rejko" uniqKey="Krueger R" first="Rejko" last="Krueger">Rejko Krueger</name></region><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</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="Singapour"><noRegion><name sortKey="Tan, Eng Ing" sort="Tan, Eng Ing" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name></noRegion><name sortKey="Tan, Eng Ing" sort="Tan, Eng Ing" 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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|area= ParkinsonV1
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|étape= Analysis
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|texte= Non‐replication of association for six polymorphisms from meta‐analysis of genome‐wide association studies of Parkinson's disease: Large‐scale collaborative study
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