Large-scale replication and heterogeneity in Parkinson disease genetic loci
Identifieur interne : 001189 ( Main/Exploration ); précédent : 001188; suivant : 001190Large-scale replication and heterogeneity in Parkinson disease genetic loci
Auteurs : Manu Sharma ; John P. A. Ioannidis ; Jan O. Aasly ; Grazia Annesi ; Alexis Brice ; Christine Van Broeckhoven ; Lars Bertram ; Maria Bozi ; David Crosiers ; Carl Clarke ; Maurizio Facheris ; Matthew Farrer ; Gaetan Garraux ; Suzana Gispert ; Georg Auburger ; Carles Vilari O-Güell ; Georgios M. Hadjigeorgiou ; Andrew A. Hicks ; Nobutaka Hattori ; Beom Jeon ; Suzanne Lesage ; Christina M. Lill ; Juei-Jueng Lin ; Timothy Lynch ; Peter Lichtner ; Anthony E. Lang ; Vincent Mok ; Barbara Jasinska-Myga ; George D. Mellick ; Karen E. Morrison ; Grzegorz Opala ; Peter P. Pramstaller ; Irene Pichler ; Sung Sup Park ; Aldo Quattrone ; Ekaterina Rogaeva ; Owen A. Ross ; Leonidas Stefanis ; Joanne D. Stockton ; Wataru Satake ; Peter A. Silburn ; Jessie Theuns ; Eng-King Tan ; Tatsushi Toda ; Hiroyuki Tomiyama ; Ryan J. Uitti ; Karin Wirdefeldt ; Zbigniew Wszolek ; Georgia Xiromerisiou ; Kuo-Chu Yueh ; Yi Zhao ; Thomas Gasser ; Demetrius Maraganore ; Rejko KrügerSource :
- Neurology [ 0028-3878 ] ; 2012.
Abstract
Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.
Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.
In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 (
Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.
Url:
DOI: 10.1212/WNL.0b013e318264e353
PubMed: 22786590
PubMed Central: 3414661
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Large-scale replication and heterogeneity in Parkinson disease genetic loci</title><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name></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></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O." last="Aasly">Jan O. Aasly</name></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></author><author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name></author><author><name sortKey="Bertram, Lars" sort="Bertram, Lars" uniqKey="Bertram L" first="Lars" last="Bertram">Lars Bertram</name></author><author><name sortKey="Bozi, Maria" sort="Bozi, Maria" uniqKey="Bozi M" first="Maria" last="Bozi">Maria Bozi</name></author><author><name sortKey="Crosiers, David" sort="Crosiers, David" uniqKey="Crosiers D" first="David" last="Crosiers">David Crosiers</name></author><author><name sortKey="Clarke, Carl" sort="Clarke, Carl" uniqKey="Clarke C" first="Carl" last="Clarke">Carl Clarke</name></author><author><name sortKey="Facheris, Maurizio" sort="Facheris, Maurizio" uniqKey="Facheris M" first="Maurizio" last="Facheris">Maurizio Facheris</name></author><author><name sortKey="Farrer, Matthew" sort="Farrer, Matthew" uniqKey="Farrer M" first="Matthew" last="Farrer">Matthew Farrer</name></author><author><name sortKey="Garraux, Gaetan" sort="Garraux, Gaetan" uniqKey="Garraux G" first="Gaetan" last="Garraux">Gaetan Garraux</name></author><author><name sortKey="Gispert, Suzana" sort="Gispert, Suzana" uniqKey="Gispert S" first="Suzana" last="Gispert">Suzana Gispert</name></author><author><name sortKey="Auburger, Georg" sort="Auburger, Georg" uniqKey="Auburger G" first="Georg" last="Auburger">Georg Auburger</name></author><author><name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name></author><author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name></author><author><name sortKey="Hicks, Andrew A" sort="Hicks, Andrew A" uniqKey="Hicks A" first="Andrew A." last="Hicks">Andrew A. Hicks</name></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name></author><author><name sortKey="Jeon, Beom" sort="Jeon, Beom" uniqKey="Jeon B" first="Beom" last="Jeon">Beom Jeon</name></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name></author><author><name sortKey="Lill, Christina M" sort="Lill, Christina M" uniqKey="Lill C" first="Christina M." last="Lill">Christina M. Lill</name></author><author><name sortKey="Lin, Juei Jueng" sort="Lin, Juei Jueng" uniqKey="Lin J" first="Juei-Jueng" last="Lin">Juei-Jueng Lin</name></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name></author><author><name sortKey="Lichtner, Peter" sort="Lichtner, Peter" uniqKey="Lichtner P" first="Peter" last="Lichtner">Peter Lichtner</name></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name></author><author><name sortKey="Mok, Vincent" sort="Mok, Vincent" uniqKey="Mok V" first="Vincent" last="Mok">Vincent Mok</name></author><author><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name></author><author><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D." last="Mellick">George D. Mellick</name></author><author><name sortKey="Morrison, Karen E" sort="Morrison, Karen E" uniqKey="Morrison K" first="Karen E." last="Morrison">Karen E. Morrison</name></author><author><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name></author><author><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P." last="Pramstaller">Peter P. Pramstaller</name></author><author><name sortKey="Pichler, Irene" sort="Pichler, Irene" uniqKey="Pichler I" first="Irene" last="Pichler">Irene Pichler</name></author><author><name sortKey="Park, Sung Sup" sort="Park, Sung Sup" uniqKey="Park S" first="Sung Sup" last="Park">Sung Sup Park</name></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name></author><author><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name></author><author><name sortKey="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</name></author><author><name sortKey="Stockton, Joanne D" sort="Stockton, Joanne D" uniqKey="Stockton J" first="Joanne D." last="Stockton">Joanne D. Stockton</name></author><author><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name></author><author><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name></author><author><name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name></author><author><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name></author><author><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name></author><author><name sortKey="Tomiyama, Hiroyuki" sort="Tomiyama, Hiroyuki" uniqKey="Tomiyama H" first="Hiroyuki" last="Tomiyama">Hiroyuki Tomiyama</name></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J." last="Uitti">Ryan J. Uitti</name></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name></author><author><name sortKey="Wszolek, Zbigniew" sort="Wszolek, Zbigniew" uniqKey="Wszolek Z" first="Zbigniew" last="Wszolek">Zbigniew Wszolek</name></author><author><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name></author><author><name sortKey="Yueh, Kuo Chu" sort="Yueh, Kuo Chu" uniqKey="Yueh K" first="Kuo-Chu" last="Yueh">Kuo-Chu Yueh</name></author><author><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name></author><author><name sortKey="Maraganore, Demetrius" sort="Maraganore, Demetrius" uniqKey="Maraganore D" first="Demetrius" last="Maraganore">Demetrius Maraganore</name></author><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22786590</idno><idno type="pmc">3414661</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414661</idno><idno type="RBID">PMC:3414661</idno><idno type="doi">10.1212/WNL.0b013e318264e353</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000048</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000048</idno><idno type="wicri:Area/Pmc/Curation">000048</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000048</idno><idno type="wicri:Area/Pmc/Checkpoint">000805</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000805</idno><idno type="wicri:Area/Ncbi/Merge">001198</idno><idno type="wicri:Area/Ncbi/Curation">001198</idno><idno type="wicri:Area/Ncbi/Checkpoint">001198</idno><idno type="wicri:doubleKey">0028-3878:2012:Sharma M:large:scale:replication</idno><idno type="wicri:Area/Main/Merge">001213</idno><idno type="wicri:Area/Main/Curation">001189</idno><idno type="wicri:Area/Main/Exploration">001189</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Large-scale replication and heterogeneity in Parkinson disease genetic loci</title><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name></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></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O." last="Aasly">Jan O. Aasly</name></author><author><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></author><author><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name></author><author><name sortKey="Bertram, Lars" sort="Bertram, Lars" uniqKey="Bertram L" first="Lars" last="Bertram">Lars Bertram</name></author><author><name sortKey="Bozi, Maria" sort="Bozi, Maria" uniqKey="Bozi M" first="Maria" last="Bozi">Maria Bozi</name></author><author><name sortKey="Crosiers, David" sort="Crosiers, David" uniqKey="Crosiers D" first="David" last="Crosiers">David Crosiers</name></author><author><name sortKey="Clarke, Carl" sort="Clarke, Carl" uniqKey="Clarke C" first="Carl" last="Clarke">Carl Clarke</name></author><author><name sortKey="Facheris, Maurizio" sort="Facheris, Maurizio" uniqKey="Facheris M" first="Maurizio" last="Facheris">Maurizio Facheris</name></author><author><name sortKey="Farrer, Matthew" sort="Farrer, Matthew" uniqKey="Farrer M" first="Matthew" last="Farrer">Matthew Farrer</name></author><author><name sortKey="Garraux, Gaetan" sort="Garraux, Gaetan" uniqKey="Garraux G" first="Gaetan" last="Garraux">Gaetan Garraux</name></author><author><name sortKey="Gispert, Suzana" sort="Gispert, Suzana" uniqKey="Gispert S" first="Suzana" last="Gispert">Suzana Gispert</name></author><author><name sortKey="Auburger, Georg" sort="Auburger, Georg" uniqKey="Auburger G" first="Georg" last="Auburger">Georg Auburger</name></author><author><name sortKey="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name></author><author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name></author><author><name sortKey="Hicks, Andrew A" sort="Hicks, Andrew A" uniqKey="Hicks A" first="Andrew A." last="Hicks">Andrew A. Hicks</name></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name></author><author><name sortKey="Jeon, Beom" sort="Jeon, Beom" uniqKey="Jeon B" first="Beom" last="Jeon">Beom Jeon</name></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name></author><author><name sortKey="Lill, Christina M" sort="Lill, Christina M" uniqKey="Lill C" first="Christina M." last="Lill">Christina M. Lill</name></author><author><name sortKey="Lin, Juei Jueng" sort="Lin, Juei Jueng" uniqKey="Lin J" first="Juei-Jueng" last="Lin">Juei-Jueng Lin</name></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name></author><author><name sortKey="Lichtner, Peter" sort="Lichtner, Peter" uniqKey="Lichtner P" first="Peter" last="Lichtner">Peter Lichtner</name></author><author><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name></author><author><name sortKey="Mok, Vincent" sort="Mok, Vincent" uniqKey="Mok V" first="Vincent" last="Mok">Vincent Mok</name></author><author><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name></author><author><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D." last="Mellick">George D. Mellick</name></author><author><name sortKey="Morrison, Karen E" sort="Morrison, Karen E" uniqKey="Morrison K" first="Karen E." last="Morrison">Karen E. Morrison</name></author><author><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name></author><author><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P." last="Pramstaller">Peter P. Pramstaller</name></author><author><name sortKey="Pichler, Irene" sort="Pichler, Irene" uniqKey="Pichler I" first="Irene" last="Pichler">Irene Pichler</name></author><author><name sortKey="Park, Sung Sup" sort="Park, Sung Sup" uniqKey="Park S" first="Sung Sup" last="Park">Sung Sup Park</name></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name></author><author><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name></author><author><name sortKey="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</name></author><author><name sortKey="Stockton, Joanne D" sort="Stockton, Joanne D" uniqKey="Stockton J" first="Joanne D." last="Stockton">Joanne D. Stockton</name></author><author><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name></author><author><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name></author><author><name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name></author><author><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name></author><author><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name></author><author><name sortKey="Tomiyama, Hiroyuki" sort="Tomiyama, Hiroyuki" uniqKey="Tomiyama H" first="Hiroyuki" last="Tomiyama">Hiroyuki Tomiyama</name></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J." last="Uitti">Ryan J. Uitti</name></author><author><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name></author><author><name sortKey="Wszolek, Zbigniew" sort="Wszolek, Zbigniew" uniqKey="Wszolek Z" first="Zbigniew" last="Wszolek">Zbigniew Wszolek</name></author><author><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name></author><author><name sortKey="Yueh, Kuo Chu" sort="Yueh, Kuo Chu" uniqKey="Yueh K" first="Kuo-Chu" last="Yueh">Kuo-Chu Yueh</name></author><author><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name></author><author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name></author><author><name sortKey="Maraganore, Demetrius" sort="Maraganore, Demetrius" uniqKey="Maraganore D" first="Demetrius" last="Maraganore">Demetrius Maraganore</name></author><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name></author></analytic><series><title level="j">Neurology</title><idno type="ISSN">0028-3878</idno><idno type="eISSN">1526-632X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective:</title><p>Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.</p></sec><sec><title>Methods:</title><p>Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.</p></sec><sec><title>Results:</title><p>In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 (<italic>LAMP3</italic>, <italic>BST1</italic>, and <italic>MAPT</italic>) and susceptibility per-allele odds ratios of 1.14–1.43 (<italic>STK39</italic>, <italic>GAK</italic>, <italic>SNCA</italic>, <italic>LRRK2</italic>, <italic>SYT11</italic>, and <italic>HIP1R</italic>). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (<italic>I</italic><sup>2</sup> estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the <italic>BST1</italic> (rs11724635) in Asian vs Caucasian populations and similar effects for <italic>SNCA</italic>, <italic>LRRK2</italic>, <italic>LAMP3</italic>, <italic>HIP1R</italic>, and <italic>STK39</italic> in Asian and Caucasian populations, while <italic>MAPT</italic> rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD.</p></sec><sec><title>Conclusion:</title><p>Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. <italic>Neurology</italic>® 2012;79:659–667</p></sec></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O." last="Aasly">Jan O. Aasly</name><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><name sortKey="Auburger, Georg" sort="Auburger, Georg" uniqKey="Auburger G" first="Georg" last="Auburger">Georg Auburger</name><name sortKey="Bertram, Lars" sort="Bertram, Lars" uniqKey="Bertram L" first="Lars" last="Bertram">Lars Bertram</name><name sortKey="Bozi, Maria" sort="Bozi, Maria" uniqKey="Bozi M" first="Maria" last="Bozi">Maria Bozi</name><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><name sortKey="Clarke, Carl" sort="Clarke, Carl" uniqKey="Clarke C" first="Carl" last="Clarke">Carl Clarke</name><name sortKey="Crosiers, David" sort="Crosiers, David" uniqKey="Crosiers D" first="David" last="Crosiers">David Crosiers</name><name sortKey="Facheris, Maurizio" sort="Facheris, Maurizio" uniqKey="Facheris M" first="Maurizio" last="Facheris">Maurizio Facheris</name><name sortKey="Farrer, Matthew" sort="Farrer, Matthew" uniqKey="Farrer M" first="Matthew" last="Farrer">Matthew Farrer</name><name sortKey="Garraux, Gaetan" sort="Garraux, Gaetan" uniqKey="Garraux G" first="Gaetan" last="Garraux">Gaetan Garraux</name><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><name sortKey="Gispert, Suzana" sort="Gispert, Suzana" uniqKey="Gispert S" first="Suzana" last="Gispert">Suzana Gispert</name><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><name sortKey="Hicks, Andrew A" sort="Hicks, Andrew A" uniqKey="Hicks A" first="Andrew A." last="Hicks">Andrew A. Hicks</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="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name><name sortKey="Jeon, Beom" sort="Jeon, Beom" uniqKey="Jeon B" first="Beom" last="Jeon">Beom Jeon</name><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name><name sortKey="Lichtner, Peter" sort="Lichtner, Peter" uniqKey="Lichtner P" first="Peter" last="Lichtner">Peter Lichtner</name><name sortKey="Lill, Christina M" sort="Lill, Christina M" uniqKey="Lill C" first="Christina M." last="Lill">Christina M. Lill</name><name sortKey="Lin, Juei Jueng" sort="Lin, Juei Jueng" uniqKey="Lin J" first="Juei-Jueng" last="Lin">Juei-Jueng Lin</name><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name><name sortKey="Maraganore, Demetrius" sort="Maraganore, Demetrius" uniqKey="Maraganore D" first="Demetrius" last="Maraganore">Demetrius Maraganore</name><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D." last="Mellick">George D. Mellick</name><name sortKey="Mok, Vincent" sort="Mok, Vincent" uniqKey="Mok V" first="Vincent" last="Mok">Vincent Mok</name><name sortKey="Morrison, Karen E" sort="Morrison, Karen E" uniqKey="Morrison K" first="Karen E." last="Morrison">Karen E. Morrison</name><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name><name sortKey="Park, Sung Sup" sort="Park, Sung Sup" uniqKey="Park S" first="Sung Sup" last="Park">Sung Sup Park</name><name sortKey="Pichler, Irene" sort="Pichler, Irene" uniqKey="Pichler I" first="Irene" last="Pichler">Irene Pichler</name><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P." last="Pramstaller">Peter P. Pramstaller</name><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name><name sortKey="Rogaeva, Ekaterina" sort="Rogaeva, Ekaterina" uniqKey="Rogaeva E" first="Ekaterina" last="Rogaeva">Ekaterina Rogaeva</name><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name><name sortKey="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</name><name sortKey="Stockton, Joanne D" sort="Stockton, Joanne D" uniqKey="Stockton J" first="Joanne D." last="Stockton">Joanne D. Stockton</name><name sortKey="Tan, Eng King" sort="Tan, Eng King" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name><name sortKey="Theuns, Jessie" sort="Theuns, Jessie" uniqKey="Theuns J" first="Jessie" last="Theuns">Jessie Theuns</name><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name><name sortKey="Tomiyama, Hiroyuki" sort="Tomiyama, Hiroyuki" uniqKey="Tomiyama H" first="Hiroyuki" last="Tomiyama">Hiroyuki Tomiyama</name><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J." last="Uitti">Ryan J. Uitti</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="Vilari O Guell, Carles" sort="Vilari O Guell, Carles" uniqKey="Vilari O Guell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name><name sortKey="Wszolek, Zbigniew" sort="Wszolek, Zbigniew" uniqKey="Wszolek Z" first="Zbigniew" last="Wszolek">Zbigniew Wszolek</name><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name><name sortKey="Yueh, Kuo Chu" sort="Yueh, Kuo Chu" uniqKey="Yueh K" first="Kuo-Chu" last="Yueh">Kuo-Chu Yueh</name><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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