Independent and joint effects of the MAPT and SNCA genes in Parkinson disease
Identifieur interne : 000027 ( France/Analysis ); précédent : 000026; suivant : 000028Independent and joint effects of the MAPT and SNCA genes in Parkinson disease
Auteurs : Alexis Elbaz [France] ; Owen A. Ross [États-Unis] ; John P. A. Ioannidis [Grèce, États-Unis] ; Alexandra I. Soto-Ortolaza [États-Unis] ; Frédéric Moisan [France] ; Jan Aasly [Norvège] ; Grazia Annesi [Italie] ; Maria Bozi [Grèce] ; Laura Brighina [Italie] ; Marie-Christine Chartier-Harlin [France] ; Alain Destée [France] ; Carlo Ferrarese [Italie] ; Alessandro Ferraris [Italie] ; J. Mark Gibson [Irlande (pays)] ; Suzana Gispert [Allemagne] ; Georgios M. Hadjigeorgiou [Grèce] ; Barbara Jasinska-Myga [Pologne] ; Christine Klein [Allemagne] ; Rejko Krüger [Allemagne] ; Jean-Charles Lambert [France] ; Katja Lohmann [Allemagne] ; Simone Van De Loo [Allemagne] ; Marie-Anne Loriot [France] ; Timothy Lynch [Irlande (pays)] ; George D. Mellick [Australie] ; Eugénie Mutez [France] ; Christer Nilsson [Suède] ; Grzegorz Opala [Pologne] ; Andreas Puschmann [Suède] ; Aldo Quattrone [Italie] ; Manu Sharma [Allemagne] ; Peter A. Silburn [Australie] ; Leonidas Stefanis [Grèce] ; Ryan J. Uitti [États-Unis] ; Enza Maria Valente [Italie] ; Carles Vilari O-Güell [États-Unis, Canada] ; Karin Wirdefeldt [Suède] ; Zbigniew K. Wszolek [États-Unis] ; Georgia Xiromerisiou [Grèce] ; Demetrius M. Maraganore [États-Unis] ; Matthew J. Farrer [États-Unis, Canada]Source :
- Annals of Neurology [ 0364-5134 ] ; 2011-05.
Abstract
Objective:: We studied the independent and joint effects of the genes encoding alpha‐synuclein (SNCA) and microtubule‐associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta‐analysis of individual data from case–control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO‐PD) consortium. Methods:: Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed‐ and random‐effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case–control and case‐only approach. Results:: Fifteen GEO‐PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1‐haplotype–defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3′ end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. Interpretation:: This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects. ANN NEUROL 2011
Url:
DOI: 10.1002/ana.22321
Affiliations:
- Allemagne, Australie, Canada, France, Grèce, Irlande (pays), Italie, Norvège, Pologne, Suède, États-Unis
- Bade-Wurtemberg, District de Tübingen, Floride, Illinois, Massachusetts, Nord-Pas-de-Calais, Svealand, Trøndelag, Île-de-France
- Lille, Paris, Stockholm, Trondheim, Tübingen
- Université Lille 2, Université Lille Nord de France
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xml:lang="fr">Grèce</country><wicri:regionArea>General Hospital of Syros, Syros, and Second Department of Neurology, University of Athens Medical School, Athens</wicri:regionArea><wicri:noRegion>Athens</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"><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurology and Neuroscience, University of Milano‐Bicocca, San Gerardo Hospital, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation></author><author><name sortKey="Chartier Arlin, Marie Hristine" sort="Chartier Arlin, Marie Hristine" uniqKey="Chartier Arlin M" first="Marie-Christine" last="Chartier-Harlin">Marie-Christine Chartier-Harlin</name><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>UMR 837 INSERM, Lille</wicri:regionArea><placeName><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Univ Lille Nord de France, Lille</wicri:regionArea><placeName><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destée">Alain Destée</name><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>UMR 837 INSERM, Lille</wicri:regionArea><placeName><settlement type="city">Lille</settlement></placeName><placeName><settlement type="city">Lille</settlement><region type="region" nuts="2">Nord-Pas-de-Calais</region></placeName><orgName type="university" n="3">Université Lille 2</orgName><orgName type="institution" wicri:auto="newGroup">Université Lille Nord de France</orgName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Univ Lille Nord de France, Lille</wicri:regionArea><placeName><settlement type="city">Lille</settlement></placeName><placeName><settlement type="city">Lille</settlement><region type="region" nuts="2">Nord-Pas-de-Calais</region></placeName><orgName type="university" n="3">Université Lille 2</orgName><orgName type="institution" wicri:auto="newGroup">Université Lille Nord de France</orgName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>University Hospital, CHRU, Lille</wicri:regionArea><placeName><settlement type="city">Lille</settlement></placeName><placeName><settlement type="city">Lille</settlement><region type="region" nuts="2">Nord-Pas-de-Calais</region></placeName><orgName type="university" n="3">Université Lille 2</orgName><orgName type="institution" wicri:auto="newGroup">Université Lille Nord de France</orgName></affiliation></author><author><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Neurology and Neuroscience, University of Milano‐Bicocca, San Gerardo Hospital, Monza</wicri:regionArea><wicri:noRegion>Monza</wicri:noRegion></affiliation></author><author><name sortKey="Ferraris, Alessandro" sort="Ferraris, Alessandro" uniqKey="Ferraris A" first="Alessandro" last="Ferraris">Alessandro Ferraris</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Mendel Laboratory IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo</wicri:regionArea><wicri:noRegion>San Giovanni Rotondo</wicri:noRegion></affiliation></author><author><name sortKey="Gibson, J Mark" sort="Gibson, J Mark" uniqKey="Gibson J" first="J. Mark" last="Gibson">J. Mark Gibson</name><affiliation wicri:level="1"><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Department of Neurology, Royal Victoria Hospital, Belfast</wicri:regionArea><wicri:noRegion>Belfast</wicri:noRegion></affiliation></author><author><name sortKey="Gispert, Suzana" sort="Gispert, Suzana" uniqKey="Gispert S" first="Suzana" last="Gispert">Suzana Gispert</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, Goethe University, Frankfurt am Main</wicri:regionArea><wicri:noRegion>Frankfurt am Main</wicri:noRegion><wicri:noRegion>Frankfurt am Main</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"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of Neurology, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly, Larissa</wicri:regionArea><wicri:noRegion>Larissa</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Institute of Biomedical Research and Technology, CERETETH, Larissa</wicri:regionArea><wicri:noRegion>Larissa</wicri:noRegion></affiliation></author><author><name sortKey="Jasinska Yga, Barbara" sort="Jasinska Yga, Barbara" uniqKey="Jasinska Yga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name><affiliation wicri:level="1"><country xml:lang="fr">Pologne</country><wicri:regionArea>Department of Neurology, Medical University of Silesia, Katowice</wicri:regionArea><wicri:noRegion>Katowice</wicri:noRegion></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck</wicri:regionArea><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases, Tübingen</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="Lambert, Jean Harles" sort="Lambert, Jean Harles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U744, Pasteur Institute from Lille, University of Lille‐Nord de France, Lille</wicri:regionArea><placeName><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Lohmann, Katja" sort="Lohmann, Katja" uniqKey="Lohmann K" first="Katja" last="Lohmann">Katja Lohmann</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck, Lübeck</wicri:regionArea><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Van De Loo, Simone" sort="Van De Loo, Simone" uniqKey="Van De Loo S" first="Simone" last="Van De Loo">Simone Van De Loo</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurology, Goethe University, Frankfurt am Main</wicri:regionArea><wicri:noRegion>Frankfurt am Main</wicri:noRegion><wicri:noRegion>Frankfurt am Main</wicri:noRegion></affiliation></author><author><name sortKey="Loriot, Marie Nne" sort="Loriot, Marie Nne" uniqKey="Loriot M" first="Marie-Anne" last="Loriot">Marie-Anne Loriot</name><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMR‐S 775, Molecular basis of response to xenobiotics, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>University Paris Descartes, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Assistance‐Publique Hôpitaux de Paris, Georges Pompidou European Hospital (HEGP), Department of Biochemistry, Pharmacogenetics and Molecular Oncology, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name><affiliation wicri:level="1"><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Dublin Neurological Institute at the Mater Misericordiae University Hospital and Conway Institute of Biomolecular and Biomedical Research, University College, Dublin</wicri:regionArea><wicri:noRegion>Dublin</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"><country xml:lang="fr">Australie</country><wicri:regionArea>National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Neurology Research Centre, Royal Brisbane and Women's Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Mutez, Eugenie" sort="Mutez, Eugenie" uniqKey="Mutez E" first="Eugénie" last="Mutez">Eugénie Mutez</name><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>UMR 837 INSERM, Lille</wicri:regionArea><placeName><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Univ Lille Nord de France, Lille</wicri:regionArea><placeName><settlement type="city">Lille</settlement></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>University Hospital, CHRU, Lille</wicri:regionArea><placeName><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Nilsson, Christer" sort="Nilsson, Christer" uniqKey="Nilsson C" first="Christer" last="Nilsson">Christer Nilsson</name><affiliation wicri:level="1"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Science, Section of Geriatric Psychiatry, Lund University, Lund</wicri:regionArea><wicri:noRegion>Lund</wicri:noRegion></affiliation></author><author><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name><affiliation wicri:level="1"><country xml:lang="fr">Pologne</country><wicri:regionArea>Department of Neurology, Medical University of Silesia, Katowice</wicri:regionArea><wicri:noRegion>Katowice</wicri:noRegion></affiliation></author><author><name sortKey="Puschmann, Andreas" sort="Puschmann, Andreas" uniqKey="Puschmann A" first="Andreas" last="Puschmann">Andreas Puschmann</name><affiliation wicri:level="1"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Science, Section of Geriatric Psychiatry, Lund University, Lund</wicri:regionArea><wicri:noRegion>Lund</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neurology, Skåne University Hospital, Lund</wicri:regionArea><wicri:noRegion>Lund</wicri:noRegion></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 and Neuroimaging Research Unit, National Research Council, Germaneto</wicri:regionArea><wicri:noRegion>Germaneto</wicri:noRegion></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>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases, Tübingen</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>National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Neurology Research Centre, Royal Brisbane and Women's Hospital, Brisbane, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>School of Medicine and Centre for Clinical Research, University of Queensland, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens and Second Department of Neurology, University of Athens Medical School, Athens</wicri:regionArea><wicri:noRegion>Athens</wicri:noRegion></affiliation></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J." last="Uitti">Ryan J. Uitti</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Department of Neurology, Mayo Clinic, Jacksonville</wicri:cityArea></affiliation></author><author><name sortKey="Valente, Enza Maria" sort="Valente, Enza Maria" uniqKey="Valente E" first="Enza Maria" last="Valente">Enza Maria Valente</name><affiliation wicri:level="1"><country xml:lang="fr">Italie</country><wicri:regionArea>Mendel Laboratory IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo</wicri:regionArea><wicri:noRegion>San Giovanni Rotondo</wicri:noRegion></affiliation></author><author><name sortKey="Vilari O Ell, Carles" sort="Vilari O Ell, Carles" uniqKey="Vilari O Ell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville</wicri:cityArea></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</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 Clinical Neuroscience and 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="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Department of Neurology, Mayo Clinic, Jacksonville</wicri:cityArea></affiliation></author><author><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Department of Neurology, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly, Larissa</wicri:regionArea><wicri:noRegion>Larissa</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Grèce</country><wicri:regionArea>Institute of Biomedical Research and Technology, CERETETH, Larissa</wicri:regionArea><wicri:noRegion>Larissa</wicri:noRegion></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"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Neurology, NorthShore University HealthSystem, Evanston</wicri:cityArea></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville</wicri:cityArea></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-05">2011-05</date><biblScope unit="volume">69</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="778">778</biblScope><biblScope unit="page" to="792">792</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">E4A05E8C03AFAA6BA06C06A7DEAF7FC3992FC948</idno><idno type="DOI">10.1002/ana.22321</idno><idno type="ArticleID">ANA22321</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective:: We studied the independent and joint effects of the genes encoding alpha‐synuclein (SNCA) and microtubule‐associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta‐analysis of individual data from case–control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO‐PD) consortium. Methods:: Participants of Caucasian ancestry were genotyped for a total of 4 SNCA (rs2583988, rs181489, rs356219, rs11931074) and 2 MAPT (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of SNCA and MAPT SNPs were investigated using fixed‐ and random‐effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case–control and case‐only approach. Results:: Fifteen GEO‐PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 SNCA SNPs and the MAPT H1‐haplotype–defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For SNCA, the strongest associations were observed for SNPs located at the 3′ end of the gene. There was no evidence of statistical interaction between any of the 4 SNCA SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale. Interpretation:: This study confirms the association between PD and both SNCA SNPs and the H1 MAPT haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects. ANN NEUROL 2011</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Canada</li><li>France</li><li>Grèce</li><li>Irlande (pays)</li><li>Italie</li><li>Norvège</li><li>Pologne</li><li>Suède</li><li>États-Unis</li></country><region><li>Bade-Wurtemberg</li><li>District de Tübingen</li><li>Floride</li><li>Illinois</li><li>Massachusetts</li><li>Nord-Pas-de-Calais</li><li>Svealand</li><li>Trøndelag</li><li>Île-de-France</li></region><settlement><li>Lille</li><li>Paris</li><li>Stockholm</li><li>Trondheim</li><li>Tübingen</li></settlement><orgName><li>Université Lille 2</li><li>Université Lille Nord de France</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name></region><name sortKey="Chartier Arlin, Marie Hristine" sort="Chartier Arlin, Marie Hristine" uniqKey="Chartier Arlin M" first="Marie-Christine" last="Chartier-Harlin">Marie-Christine Chartier-Harlin</name><name sortKey="Chartier Arlin, Marie Hristine" sort="Chartier Arlin, Marie Hristine" uniqKey="Chartier Arlin M" first="Marie-Christine" last="Chartier-Harlin">Marie-Christine Chartier-Harlin</name><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destée">Alain Destée</name><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destée">Alain Destée</name><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destée">Alain Destée</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="Loriot, Marie Nne" sort="Loriot, Marie Nne" uniqKey="Loriot M" first="Marie-Anne" last="Loriot">Marie-Anne Loriot</name><name sortKey="Loriot, Marie Nne" sort="Loriot, Marie Nne" uniqKey="Loriot M" first="Marie-Anne" last="Loriot">Marie-Anne Loriot</name><name sortKey="Loriot, Marie Nne" sort="Loriot, Marie Nne" uniqKey="Loriot M" first="Marie-Anne" last="Loriot">Marie-Anne Loriot</name><name sortKey="Moisan, Frederic" sort="Moisan, Frederic" uniqKey="Moisan F" first="Frédéric" last="Moisan">Frédéric Moisan</name><name sortKey="Moisan, Frederic" sort="Moisan, Frederic" uniqKey="Moisan F" first="Frédéric" last="Moisan">Frédéric Moisan</name><name sortKey="Mutez, Eugenie" sort="Mutez, Eugenie" uniqKey="Mutez E" first="Eugénie" last="Mutez">Eugénie Mutez</name><name sortKey="Mutez, Eugenie" sort="Mutez, Eugenie" uniqKey="Mutez E" first="Eugénie" last="Mutez">Eugénie Mutez</name><name sortKey="Mutez, Eugenie" sort="Mutez, Eugenie" uniqKey="Mutez E" first="Eugénie" last="Mutez">Eugénie Mutez</name></country><country name="États-Unis"><region name="Floride"><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name></region><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</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="Maraganore, Demetrius M" sort="Maraganore, Demetrius M" uniqKey="Maraganore D" first="Demetrius M." last="Maraganore">Demetrius M. Maraganore</name><name sortKey="Soto Rtolaza, Alexandra I" sort="Soto Rtolaza, Alexandra I" uniqKey="Soto Rtolaza A" first="Alexandra I." last="Soto-Ortolaza">Alexandra I. Soto-Ortolaza</name><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J." last="Uitti">Ryan J. Uitti</name><name sortKey="Vilari O Ell, Carles" sort="Vilari O Ell, Carles" uniqKey="Vilari O Ell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name></country><country name="Grèce"><noRegion><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></noRegion><name sortKey="Bozi, Maria" sort="Bozi, Maria" uniqKey="Bozi M" first="Maria" last="Bozi">Maria Bozi</name><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="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</name><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name></country><country name="Norvège"><region name="Trøndelag"><name sortKey="Aasly, Jan" sort="Aasly, Jan" uniqKey="Aasly J" first="Jan" last="Aasly">Jan Aasly</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="Ferraris, Alessandro" sort="Ferraris, Alessandro" uniqKey="Ferraris A" first="Alessandro" last="Ferraris">Alessandro Ferraris</name><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name><name sortKey="Valente, Enza Maria" sort="Valente, Enza Maria" uniqKey="Valente E" first="Enza Maria" last="Valente">Enza Maria Valente</name></country><country name="Irlande (pays)"><noRegion><name sortKey="Gibson, J Mark" sort="Gibson, J Mark" uniqKey="Gibson J" first="J. Mark" last="Gibson">J. Mark Gibson</name></noRegion><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</name></country><country name="Allemagne"><noRegion><name sortKey="Gispert, Suzana" sort="Gispert, Suzana" uniqKey="Gispert S" first="Suzana" last="Gispert">Suzana Gispert</name></noRegion><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name><name sortKey="Lohmann, Katja" sort="Lohmann, Katja" uniqKey="Lohmann K" first="Katja" last="Lohmann">Katja Lohmann</name><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><name sortKey="Van De Loo, Simone" sort="Van De Loo, Simone" uniqKey="Van De Loo S" first="Simone" last="Van De Loo">Simone Van De Loo</name></country><country name="Pologne"><noRegion><name sortKey="Jasinska Yga, Barbara" sort="Jasinska Yga, Barbara" uniqKey="Jasinska Yga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name></noRegion><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</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="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D." last="Mellick">George D. Mellick</name><name sortKey="Mellick, George D" sort="Mellick, George D" uniqKey="Mellick G" first="George D." last="Mellick">George D. Mellick</name><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name><name sortKey="Silburn, Peter A" sort="Silburn, Peter A" uniqKey="Silburn P" first="Peter A." last="Silburn">Peter A. Silburn</name></country><country name="Suède"><noRegion><name sortKey="Nilsson, Christer" sort="Nilsson, Christer" uniqKey="Nilsson C" first="Christer" last="Nilsson">Christer Nilsson</name></noRegion><name sortKey="Puschmann, Andreas" sort="Puschmann, Andreas" uniqKey="Puschmann A" first="Andreas" last="Puschmann">Andreas Puschmann</name><name sortKey="Puschmann, Andreas" sort="Puschmann, Andreas" uniqKey="Puschmann A" first="Andreas" last="Puschmann">Andreas Puschmann</name><name sortKey="Wirdefeldt, Karin" sort="Wirdefeldt, Karin" uniqKey="Wirdefeldt K" first="Karin" last="Wirdefeldt">Karin Wirdefeldt</name></country><country name="Canada"><noRegion><name sortKey="Vilari O Ell, Carles" sort="Vilari O Ell, Carles" uniqKey="Vilari O Ell C" first="Carles" last="Vilari O-Güell">Carles Vilari O-Güell</name></noRegion><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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