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 : 000743 ( Hal/Curation ); précédent : 000742; suivant : 000744Non-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] ; Demetrius Maraganore [États-Unis] ; Grazia Annesi [Italie] ; Laura Brighina [Italie] ; Alexis Brice [France] ; Alexis Elbaz [France] ; Carlo Ferrarese [Italie] ; Georgios Hadjigeorgiou [Grèce] ; Rejko Krueger [Allemagne] ; Jean-Charles Lambert [France] ; Suzanne Lesage [France] ; Katerina Markopoulou [Grèce] ; George Mellick [Australie] ; Bram Meeus [Belgique] ; Nancy Pedersen [Suède] ; Aldo Quattrone [Italie] ; Christine Van Broeckhoven [Belgique] ; Manu Sharma [Allemagne] ; Peter Silburn [Australie] ; Eng-King Tan [Singapour] ; Karin Wirdefeldt [Suède] ; John Ioannidis [Grèce]Source :
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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DOI: 10.1002/ajmg.b.30980
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Wirdefeldt</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-110072" status="VALID"> <orgName>Department of Medical Epidemiology and Biostatistics</orgName> <orgName type="acronym">MEB</orgName> <desc> <address> <addrLine>Karolinska Institutet SE-171 77 Stockholm</addrLine> <country key="SE"></country> </address> <ref type="url">http://ki.se/ki/jsp/polopoly.jsp?d=9600&l=en</ref> </desc> <listRelation> <relation active="#struct-302344" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-302344" type="direct"><org type="institution" xml:id="struct-302344" status="VALID"> <orgName>Karolinska Institutet [Stockholm]</orgName> <desc> <address> <addrLine>Solnavägen 1, 171 77 SolnaStockholm</addrLine> <country key="SE"></country> </address> <ref type="url">http://ki.se</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>Suède</country></affiliation></author><author><name sortKey="Ioannidis, John" sort="Ioannidis, John" uniqKey="Ioannidis J" first="John" last="Ioannidis">John Ioannidis</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-130659" status="INCOMING"> <orgName>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology</orgName> <desc> <address> <addrLine>Medical School - GR-45110 Ioannina</addrLine> <country key="GR"></country> </address> </desc> <listRelation> <relation active="#struct-331747" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-331747" type="direct"><org type="institution" xml:id="struct-331747" status="INCOMING"> <orgName>University of Ioannina Medical School</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Grèce</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:inserm-00528836</idno><idno type="halId">inserm-00528836</idno><idno type="halUri">http://www.hal.inserm.fr/inserm-00528836</idno><idno type="url">http://www.hal.inserm.fr/inserm-00528836</idno><idno type="doi">10.1002/ajmg.b.30980</idno><date when="2010-01-05">2010-01-05</date><idno type="wicri:Area/Hal/Corpus">000807</idno><idno type="wicri:Area/Hal/Curation">000807</idno></publicationStmt><sourceDesc><biblStruct><analytic><title 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 wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-130659" status="INCOMING"> <orgName>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology</orgName> <desc> <address> <addrLine>Medical School - GR-45110 Ioannina</addrLine> <country key="GR"></country> </address> </desc> <listRelation> <relation active="#struct-331747" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-331747" type="direct"><org type="institution" xml:id="struct-331747" status="INCOMING"> <orgName>University of Ioannina Medical School</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Grèce</country></affiliation></author><author><name sortKey="Maraganore, Demetrius" sort="Maraganore, Demetrius" uniqKey="Maraganore D" first="Demetrius" last="Maraganore">Demetrius Maraganore</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-45655" status="INCOMING"> <orgName>Department of Neurology</orgName> <desc> <address> <addrLine>Rochester, Minnesota</addrLine> <country key="US"></country> </address> </desc> <listRelation> <relation active="#struct-306961" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-306961" type="direct"><org type="institution" xml:id="struct-306961" status="INCOMING"> <orgName>Mayo Clinic College of Medicine</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>États-Unis</country></affiliation></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-46373" status="INCOMING"> <orgName>Institute of Neurological Sciences</orgName> <desc> <address> <country key="IT"></country> </address> </desc> <listRelation> <relation active="#struct-300245" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-300245" type="direct"><org type="institution" xml:id="struct-300245" status="VALID"> <orgName>National Research Council [Italy]</orgName> <orgName type="acronym">CNR</orgName> <desc> <address> <country 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key="FR"></country> </address> </desc></org></tutelle><tutelle active="#struct-331757" type="direct"><org type="institution" xml:id="struct-331757" status="INCOMING"> <orgName>Hertie Institute for Clinical Brain Research</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Allemagne</country></affiliation></author><author><name sortKey="Silburn, Peter" sort="Silburn, Peter" uniqKey="Silburn P" first="Peter" last="Silburn">Peter Silburn</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-130666" status="INCOMING"> <orgName>Eskitis Institute for Cell and Molecular Therapies</orgName> <desc> <address> <addrLine>School of Biomolecular & Physical Sciences, Nathan, QLD</addrLine> <country key="AU"></country> </address> </desc> <listRelation> <relation active="#struct-318360" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-318360" type="direct"><org type="institution" xml:id="struct-318360" status="INCOMING"> <orgName>Griffith University</orgName> <desc> <address> <country key="AU"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Australie</country></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"><hal:affiliation type="laboratory" xml:id="struct-102366" status="INCOMING"> <orgName>Duke-NUS Graduate Medical School</orgName> <desc> <address> <country key="SG"></country> </address> </desc> <listRelation> <relation active="#struct-324644" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-324644" type="direct"><org type="institution" xml:id="struct-324644" status="INCOMING"> <orgName>Duke-NUS Graduate Medical School</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Singapour</country></affiliation></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-110072" status="VALID"> <orgName>Department of Medical Epidemiology and Biostatistics</orgName> <orgName type="acronym">MEB</orgName> <desc> <address> <addrLine>Karolinska Institutet SE-171 77 Stockholm</addrLine> <country key="SE"></country> </address> <ref type="url">http://ki.se/ki/jsp/polopoly.jsp?d=9600&l=en</ref> </desc> <listRelation> <relation active="#struct-302344" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-302344" type="direct"><org type="institution" xml:id="struct-302344" status="VALID"> <orgName>Karolinska Institutet [Stockholm]</orgName> <desc> <address> <addrLine>Solnavägen 1, 171 77 SolnaStockholm</addrLine> <country key="SE"></country> </address> <ref type="url">http://ki.se</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>Suède</country></affiliation></author><author><name sortKey="Ioannidis, John" sort="Ioannidis, John" uniqKey="Ioannidis J" first="John" last="Ioannidis">John Ioannidis</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-130659" status="INCOMING"> <orgName>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology</orgName> <desc> <address> <addrLine>Medical School - GR-45110 Ioannina</addrLine> <country key="GR"></country> </address> </desc> <listRelation> <relation active="#struct-331747" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-331747" type="direct"><org type="institution" xml:id="struct-331747" status="INCOMING"> <orgName>University of Ioannina Medical School</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation><country>Grèce</country></affiliation></author></analytic><idno type="DOI">10.1002/ajmg.b.30980</idno></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></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><hal api="V3"> <titleStmt> <title 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 role="aut"> <persName> <forename type="first">Evangelos</forename> <surname>Evangelou</surname> </persName> <idno type="halauthorid">536403</idno> <affiliation ref="#struct-130659"></affiliation> <affiliation ref="#struct-182601"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Demetrius</forename> <forename type="middle">M.</forename> <surname>Maraganore</surname> </persName> <idno type="halauthorid">214217</idno> <affiliation ref="#struct-45655"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Grazia</forename> <surname>Annesi</surname> </persName> <idno type="halauthorid">214383</idno> <affiliation ref="#struct-46373"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Laura</forename> <surname>Brighina</surname> </persName> <idno type="halauthorid">536404</idno> <affiliation ref="#struct-130662"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alexis</forename> <surname>Brice</surname> </persName> <idno type="halauthorid">183596</idno> <affiliation ref="#struct-3037"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alexis</forename> <surname>Elbaz</surname> </persName> <idno type="halauthorid">217159</idno> <affiliation ref="#struct-3066"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Carlo</forename> <surname>Ferrarese</surname> </persName> <idno type="halauthorid">214386</idno> <affiliation ref="#struct-130662"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Georgios</forename> <forename type="middle">M.</forename> <surname>Hadjigeorgiou</surname> </persName> <idno type="halauthorid">214387</idno> <affiliation ref="#struct-130664"></affiliation> <affiliation ref="#struct-130849"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Rejko</forename> <surname>Krueger</surname> </persName> <idno type="halauthorid">536405</idno> <affiliation ref="#struct-130665"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Jean-Charles</forename> <surname>Lambert</surname> </persName> <idno type="halauthorid">168733</idno> <affiliation ref="#struct-2877"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Suzanne</forename> <surname>Lesage</surname> </persName> <idno type="halauthorid">233614</idno> <affiliation ref="#struct-3037"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Katerina</forename> <surname>Markopoulou</surname> </persName> <idno type="halauthorid">536406</idno> <affiliation ref="#struct-130664"></affiliation> </author> <author role="aut"> <persName> <forename type="first">George</forename> <forename type="middle">D.</forename> <surname>Mellick</surname> </persName> <idno type="halauthorid">214393</idno> <affiliation ref="#struct-130666"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Bram</forename> <surname>Meeus</surname> </persName> <idno type="halauthorid">536407</idno> <affiliation ref="#struct-130667"></affiliation> <affiliation ref="#struct-130850"></affiliation> <affiliation ref="#struct-302250"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Nancy</forename> <forename type="middle">L.</forename> <surname>Pedersen</surname> </persName> <idno type="halauthorid">536408</idno> <affiliation ref="#struct-110072"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Aldo</forename> <surname>Quattrone</surname> </persName> <idno type="halauthorid">217174</idno> <affiliation ref="#struct-46528"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Christine</forename> <surname>Van Broeckhoven</surname> </persName> <idno type="halauthorid">214398</idno> <affiliation ref="#struct-130667"></affiliation> <affiliation ref="#struct-302250"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Manu</forename> <surname>Sharma</surname> </persName> <idno type="halauthorid">536409</idno> <affiliation ref="#struct-130665"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Peter</forename> <forename type="middle">A.</forename> <surname>Silburn</surname> </persName> <idno type="halauthorid">351418</idno> <affiliation ref="#struct-130666"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Eng-King</forename> <surname>Tan</surname> </persName> <idno type="halauthorid">217176</idno> <affiliation ref="#struct-102366"></affiliation> <affiliation ref="#struct-130669"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Karin</forename> <surname>Wirdefeldt</surname> </persName> <idno type="halauthorid">214400</idno> <affiliation ref="#struct-110072"></affiliation> </author> <author role="crp"> <persName> <forename type="first">John</forename> <forename type="middle">P. A.</forename> <surname>Ioannidis</surname> </persName> <email type="md5">86f09b9afbcb1bec904a9dc4f2e2bbc4</email> <email type="domain">cc.uoi.gr</email> <idno type="halauthorid">536410</idno> <affiliation ref="#struct-130659"></affiliation> <affiliation ref="#struct-130670"></affiliation> <affiliation ref="#struct-130855"></affiliation> </author> <editor role="depositor"> <persName> <forename>Marc</forename> <surname>Savasta</surname> </persName> <email type="md5">17a3ed21e3dd17a996152da3d29e00bb</email> <email type="domain">ujf-grenoble.fr</email> </editor> <funder>Inserm; MSA; Agence Nationale de la Recherche; Agence Francaise de Securite Sanitaire de l'Environnement et du Travail; France Parkinson; FIRB 2003 GENOPOLIS Project; National Institutes of Health (NIH) 2R01 ES10751 ES10758 AG 08724; Michael J. Fox Grants; Swedish Medical Research Council; Swedish Society of Medicine; Parkinson Foundation in Sweden; VIB Genetic Service Facility; The Biobank of the Institute Born-Bunge; Fund for Scientific Research Flanders Institute for Science and Technology - Flanders (IWT-V); Foundation for Alzheimer Research (SAO/FRMA); Interuniversity Attraction Poles Program P6/43 of the Belgian Science Policy Office, Belgium</funder> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2012-02-01 11:58:54</date> <date type="whenModified">2016-02-23 14:32:08</date> <date type="whenReleased">2012-02-02 11:39:20</date> <date type="whenProduced">2010-01-05</date> <date type="whenEndEmbargoed">9999-12-31</date> <ref type="file" target="http://www.hal.inserm.fr/inserm-00528836/document"> <date notBefore="9999-12-31"></date> </ref> <ref type="file" subtype="greenPublisher" n="1" target="http://www.hal.inserm.fr/inserm-00528836/file/Evangelou_2010_non_replication_VEditeur.pdf"> <date notBefore="9999-12-31"></date> </ref> </edition> <respStmt> <resp>contributor</resp> <name key="140382"> <persName> <forename>Marc</forename> <surname>Savasta</surname> </persName> <email type="md5">17a3ed21e3dd17a996152da3d29e00bb</email> <email type="domain">ujf-grenoble.fr</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">inserm-00528836</idno> <idno type="halUri">http://www.hal.inserm.fr/inserm-00528836</idno> <idno type="halBibtex">evangelou:inserm-00528836</idno> <idno type="halRefHtml">American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 2010, 153B (1), pp.220-8. <10.1002/ajmg.b.30980></idno> <idno type="halRef">American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 2010, 153B (1), pp.220-8. <10.1002/ajmg.b.30980></idno> </publicationStmt> <seriesStmt> <idno type="stamp" n="RIIP_LILLE">Institut Pasteur de Lille</idno> <idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno> <idno type="stamp" n="UPMC">Université Pierre et Marie Curie</idno> <idno type="stamp" n="U836" p="INSERM">Grenoble Institut des Neurosciences</idno> </seriesStmt> <notesStmt> <note type="audience" n="2">International</note> <note type="popular" n="0">No</note> <note type="peer" n="1">Yes</note> </notesStmt> <sourceDesc> <biblStruct> <analytic> <title 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 role="aut"> <persName> <forename type="first">Evangelos</forename> <surname>Evangelou</surname> </persName> <idno type="halauthorid">536403</idno> <affiliation ref="#struct-130659"></affiliation> <affiliation ref="#struct-182601"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Demetrius</forename> <forename type="middle">M.</forename> <surname>Maraganore</surname> </persName> <idno type="halauthorid">214217</idno> <affiliation ref="#struct-45655"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Grazia</forename> <surname>Annesi</surname> </persName> <idno type="halauthorid">214383</idno> <affiliation ref="#struct-46373"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Laura</forename> <surname>Brighina</surname> </persName> <idno type="halauthorid">536404</idno> <affiliation ref="#struct-130662"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alexis</forename> <surname>Brice</surname> </persName> <idno type="halauthorid">183596</idno> <affiliation ref="#struct-3037"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alexis</forename> <surname>Elbaz</surname> </persName> <idno type="halauthorid">217159</idno> <affiliation ref="#struct-3066"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Carlo</forename> <surname>Ferrarese</surname> </persName> <idno type="halauthorid">214386</idno> <affiliation ref="#struct-130662"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Georgios</forename> <forename type="middle">M.</forename> <surname>Hadjigeorgiou</surname> </persName> <idno type="halauthorid">214387</idno> <affiliation ref="#struct-130664"></affiliation> <affiliation ref="#struct-130849"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Rejko</forename> <surname>Krueger</surname> </persName> <idno type="halauthorid">536405</idno> <affiliation ref="#struct-130665"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Jean-Charles</forename> <surname>Lambert</surname> </persName> <idno type="halauthorid">168733</idno> <affiliation ref="#struct-2877"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Suzanne</forename> <surname>Lesage</surname> </persName> <idno type="halauthorid">233614</idno> <affiliation ref="#struct-3037"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Katerina</forename> <surname>Markopoulou</surname> </persName> <idno type="halauthorid">536406</idno> <affiliation ref="#struct-130664"></affiliation> </author> <author role="aut"> <persName> <forename type="first">George</forename> <forename type="middle">D.</forename> <surname>Mellick</surname> </persName> <idno type="halauthorid">214393</idno> <affiliation ref="#struct-130666"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Bram</forename> <surname>Meeus</surname> </persName> <idno type="halauthorid">536407</idno> <affiliation ref="#struct-130667"></affiliation> <affiliation ref="#struct-130850"></affiliation> <affiliation ref="#struct-302250"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Nancy</forename> <forename type="middle">L.</forename> <surname>Pedersen</surname> </persName> <idno type="halauthorid">536408</idno> <affiliation ref="#struct-110072"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Aldo</forename> <surname>Quattrone</surname> </persName> <idno type="halauthorid">217174</idno> <affiliation ref="#struct-46528"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Christine</forename> <surname>Van Broeckhoven</surname> </persName> <idno type="halauthorid">214398</idno> <affiliation ref="#struct-130667"></affiliation> <affiliation ref="#struct-302250"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Manu</forename> <surname>Sharma</surname> </persName> <idno type="halauthorid">536409</idno> <affiliation ref="#struct-130665"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Peter</forename> <forename type="middle">A.</forename> <surname>Silburn</surname> </persName> <idno type="halauthorid">351418</idno> <affiliation ref="#struct-130666"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Eng-King</forename> <surname>Tan</surname> </persName> <idno type="halauthorid">217176</idno> <affiliation ref="#struct-102366"></affiliation> <affiliation ref="#struct-130669"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Karin</forename> <surname>Wirdefeldt</surname> </persName> <idno type="halauthorid">214400</idno> <affiliation ref="#struct-110072"></affiliation> </author> <author role="crp"> <persName> <forename type="first">John</forename> <forename type="middle">P. A.</forename> <surname>Ioannidis</surname> </persName> <email type="md5">86f09b9afbcb1bec904a9dc4f2e2bbc4</email> <email type="domain">cc.uoi.gr</email> <idno type="halauthorid">536410</idno> <affiliation ref="#struct-130659"></affiliation> <affiliation ref="#struct-130670"></affiliation> <affiliation ref="#struct-130855"></affiliation> </author> </analytic> <monogr> <idno type="halJournalId" status="INCOMING">68639</idno> <title level="j">American Journal of Medical Genetics Part B Neuropsychiatric Genetics</title> <imprint> <biblScope unit="volume">153B</biblScope> <biblScope unit="issue">1</biblScope> <biblScope unit="pp">220-8</biblScope> <date type="datePub">2010-01-05</date> </imprint> </monogr> <idno type="doi">10.1002/ajmg.b.30980</idno> <idno type="pubmed">19475631</idno> <idno type="pubmedcentral">PMC4699803</idno> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="en">English</language> </langUsage> <textClass> <classCode scheme="mesh">Genome-Wide Association Study</classCode> <classCode scheme="mesh">Humans</classCode> <classCode scheme="mesh">Parkinson Disease</classCode> <classCode scheme="mesh">Polymorphism, Genetic</classCode> <classCode scheme="halDomain" n="sdv.neu">Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]</classCode> <classCode scheme="halTypology" n="ART">Journal articles</classCode> </textClass> <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.</abstract> <particDesc> <org type="consortium">Genetic Epidemiology of Parkinson's Disease (GEOPD) Consortium</org> </particDesc> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
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