Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease
Identifieur interne : 000F38 ( PascalFrancis/Curation ); précédent : 000F37; suivant : 000F39Independent 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] ; Frederic Moisan [France] ; Jan Aasly [Norvège] ; Grazia Annesi [Italie] ; Maria Bozi [Grèce] ; Laura Brighina [Italie] ; Marie-Christine Chartier-Harlin [France] ; Alain Destee [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 Kruger [Allemagne] ; Jean-Charles Lambert ; Katja Lohmann [Allemagne] ; Simone Van De Loo [Allemagne] ; Marie-Anne Loriot ; Timothy Lynch ; George D. Mellick ; Eugenie Mutez [France] ; Christer Nilsson ; Grzegorz Opala [Pologne] ; Andreas Puschmann ; Aldo Quattrone ; Manu Sharma [Allemagne] ; Peter A. Silburn ; Leonidas Stefanis ; Ryan J. Uitti ; Enza Maria Valente [Italie] ; Carles Vilarino-Güell [États-Unis] ; Karin Wirdefeldt ; Zbigniew K. Wszolek ; Georgia Xiromerisiou [Grèce] ; Demetrius M. Maraganore ; Matthew J. Farrer [États-Unis]Source :
- Annals of neurology [ 0364-5134 ] ; 2011.
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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 (rs1 052553, 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.
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Hadjigeorgiou</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Department of Neurology, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></inist:fA14><country>Grèce</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Institute of Biomedical Research and Technology, CERETETH</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></inist:fA14><country>Grèce</country></affiliation></author><author><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Department of Neurology, Medical University of Silesia</s1><s2>Katowice</s2><s3>POL</s3><sZ>17 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pologne</country></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><inist:fA14 i1="19"><s1>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>18 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Kruger">Rejko Kruger</name><affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases</s1><s2>Tübingen</s2><s3>DEU</s3><sZ>19 aut.</sZ><sZ>31 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name></author><author><name sortKey="Lohmann, Katja" sort="Lohmann, Katja" uniqKey="Lohmann K" first="Katja" last="Lohmann">Katja Lohmann</name><affiliation wicri:level="1"><inist:fA14 i1="19"><s1>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>18 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Allemagne</country></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"><inist:fA14 i1="15"><s1>Department of Neurology, Goethe University</s1><s2>Frankfurt am Main</s2><s3>DEU</s3><sZ>15 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Loriot, Marie Anne" sort="Loriot, Marie Anne" uniqKey="Loriot M" first="Marie-Anne" last="Loriot">Marie-Anne Loriot</name></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</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="Mutez, Eugenie" sort="Mutez, Eugenie" uniqKey="Mutez E" first="Eugenie" last="Mutez">Eugenie Mutez</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>UMR 837 INSERM</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Univ Lille Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>University Hospital, CHRU</s1><s2>Lille</s2><s3>FRA</s3><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Nilsson, Christer" sort="Nilsson, Christer" uniqKey="Nilsson C" first="Christer" last="Nilsson">Christer Nilsson</name></author><author><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Department of Neurology, Medical University of Silesia</s1><s2>Katowice</s2><s3>POL</s3><sZ>17 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pologne</country></affiliation></author><author><name sortKey="Puschmann, Andreas" sort="Puschmann, Andreas" uniqKey="Puschmann A" first="Andreas" last="Puschmann">Andreas Puschmann</name></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name></author><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases</s1><s2>Tübingen</s2><s3>DEU</s3><sZ>19 aut.</sZ><sZ>31 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></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="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</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="Valente, Enza Maria" sort="Valente, Enza Maria" uniqKey="Valente E" first="Enza Maria" last="Valente">Enza Maria Valente</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Mendel Laboratory IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo</s1><s3>ITA</s3><sZ>13 aut.</sZ><sZ>35 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Vilarino Guell, Carles" sort="Vilarino Guell, Carles" uniqKey="Vilarino Guell C" first="Carles" last="Vilarino-Güell">Carles Vilarino-Güell</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, FL</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>36 aut.</sZ><sZ>41 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></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 K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name></author><author><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Department of Neurology, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></inist:fA14><country>Grèce</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Institute of Biomedical Research and Technology, CERETETH</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></inist:fA14><country>Grèce</country></affiliation></author><author><name sortKey="Maraganore, Demetrius M" sort="Maraganore, Demetrius M" uniqKey="Maraganore D" first="Demetrius M." last="Maraganore">Demetrius M. Maraganore</name></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="1"><inist:fA14 i1="03"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, FL</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>36 aut.</sZ><sZ>41 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">11-0248600</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 11-0248600 INIST</idno><idno type="RBID">Pascal:11-0248600</idno><idno type="wicri:Area/PascalFrancis/Corpus">000401</idno><idno type="wicri:Area/PascalFrancis/Curation">000F38</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease</title><author><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INSERM, U708, Neuroepidemiology</s1><s2>75013, Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>UPMC Univ Paris 06, UMR-S708, Neuroepidemiology</s1><s2>75005, Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Ross, Owen A" sort="Ross, Owen A" uniqKey="Ross O" first="Owen A." last="Ross">Owen A. Ross</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, FL</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>36 aut.</sZ><sZ>41 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Ioannidis, John P A" sort="Ioannidis, John P A" uniqKey="Ioannidis J" first="John P. A." last="Ioannidis">John P. A. Ioannidis</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of loannina Medical School</s1><s2>loannina</s2><s3>GRC</s3><sZ>3 aut.</sZ></inist:fA14><country>Grèce</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Tufts Clinical and Translational Science Institute, Tufts Medical Center, and Tufts University School of Medicine</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Soto Ortolaza, Alexandra I" sort="Soto Ortolaza, Alexandra I" uniqKey="Soto Ortolaza A" first="Alexandra I." last="Soto-Ortolaza">Alexandra I. Soto-Ortolaza</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, FL</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>36 aut.</sZ><sZ>41 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Moisan, Frederic" sort="Moisan, Frederic" uniqKey="Moisan F" first="Frederic" last="Moisan">Frederic Moisan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INSERM, U708, Neuroepidemiology</s1><s2>75013, Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>UPMC Univ Paris 06, UMR-S708, Neuroepidemiology</s1><s2>75005, Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Aasly, Jan" sort="Aasly, Jan" uniqKey="Aasly J" first="Jan" last="Aasly">Jan Aasly</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Neurology, St Olav Hospital</s1><s2>Trondheim</s2><s3>NOR</s3><sZ>6 aut.</sZ></inist:fA14><country>Norvège</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"><inist:fA14 i1="07"><s1>Institute of Neurological Sciences, National Research Council</s1><s2>Cosenza</s2><s3>ITA</s3><sZ>7 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Bozi, Maria" sort="Bozi, Maria" uniqKey="Bozi M" first="Maria" last="Bozi">Maria Bozi</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>General Hospital of Syros, Syros, and Second Department of Neurology, University of Athens Medical School</s1><s2>Athens</s2><s3>GRC</s3><sZ>8 aut.</sZ></inist:fA14><country>Grèce</country></affiliation></author><author><name sortKey="Brighina, Laura" sort="Brighina, Laura" uniqKey="Brighina L" first="Laura" last="Brighina">Laura Brighina</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Neurology and Neuroscience, University of Milano-Bicocca, San Gerardo Hospital</s1><s2>Monza</s2><s3>ITA</s3><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Chartier Harlin, Marie Christine" sort="Chartier Harlin, Marie Christine" uniqKey="Chartier Harlin M" first="Marie-Christine" last="Chartier-Harlin">Marie-Christine Chartier-Harlin</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>UMR 837 INSERM</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Univ Lille Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Destee, Alain" sort="Destee, Alain" uniqKey="Destee A" first="Alain" last="Destee">Alain Destee</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>UMR 837 INSERM</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Univ Lille Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>University Hospital, CHRU</s1><s2>Lille</s2><s3>FRA</s3><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Ferrarese, Carlo" sort="Ferrarese, Carlo" uniqKey="Ferrarese C" first="Carlo" last="Ferrarese">Carlo Ferrarese</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Neurology and Neuroscience, University of Milano-Bicocca, San Gerardo Hospital</s1><s2>Monza</s2><s3>ITA</s3><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Ferraris, Alessandro" sort="Ferraris, Alessandro" uniqKey="Ferraris A" first="Alessandro" last="Ferraris">Alessandro Ferraris</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Mendel Laboratory IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo</s1><s3>ITA</s3><sZ>13 aut.</sZ><sZ>35 aut.</sZ></inist:fA14><country>Italie</country></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"><inist:fA14 i1="14"><s1>Department of Neurology, Royal Victoria Hospital</s1><s2>Belfast</s2><s3>IRL</s3><sZ>14 aut.</sZ></inist:fA14><country>Irlande (pays)</country></affiliation></author><author><name sortKey="Gispert, Suzana" sort="Gispert, Suzana" uniqKey="Gispert S" first="Suzana" last="Gispert">Suzana Gispert</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Department of Neurology, Goethe University</s1><s2>Frankfurt am Main</s2><s3>DEU</s3><sZ>15 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Department of Neurology, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></inist:fA14><country>Grèce</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Institute of Biomedical Research and Technology, CERETETH</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></inist:fA14><country>Grèce</country></affiliation></author><author><name sortKey="Jasinska Myga, Barbara" sort="Jasinska Myga, Barbara" uniqKey="Jasinska Myga B" first="Barbara" last="Jasinska-Myga">Barbara Jasinska-Myga</name><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Department of Neurology, Medical University of Silesia</s1><s2>Katowice</s2><s3>POL</s3><sZ>17 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pologne</country></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><inist:fA14 i1="19"><s1>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>18 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Kruger">Rejko Kruger</name><affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases</s1><s2>Tübingen</s2><s3>DEU</s3><sZ>19 aut.</sZ><sZ>31 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Lambert, Jean Charles" sort="Lambert, Jean Charles" uniqKey="Lambert J" first="Jean-Charles" last="Lambert">Jean-Charles Lambert</name></author><author><name sortKey="Lohmann, Katja" sort="Lohmann, Katja" uniqKey="Lohmann K" first="Katja" last="Lohmann">Katja Lohmann</name><affiliation wicri:level="1"><inist:fA14 i1="19"><s1>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>18 aut.</sZ><sZ>21 aut.</sZ></inist:fA14><country>Allemagne</country></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"><inist:fA14 i1="15"><s1>Department of Neurology, Goethe University</s1><s2>Frankfurt am Main</s2><s3>DEU</s3><sZ>15 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Loriot, Marie Anne" sort="Loriot, Marie Anne" uniqKey="Loriot M" first="Marie-Anne" last="Loriot">Marie-Anne Loriot</name></author><author><name sortKey="Lynch, Timothy" sort="Lynch, Timothy" uniqKey="Lynch T" first="Timothy" last="Lynch">Timothy Lynch</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="Mutez, Eugenie" sort="Mutez, Eugenie" uniqKey="Mutez E" first="Eugenie" last="Mutez">Eugenie Mutez</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>UMR 837 INSERM</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Univ Lille Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>University Hospital, CHRU</s1><s2>Lille</s2><s3>FRA</s3><sZ>11 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Nilsson, Christer" sort="Nilsson, Christer" uniqKey="Nilsson C" first="Christer" last="Nilsson">Christer Nilsson</name></author><author><name sortKey="Opala, Grzegorz" sort="Opala, Grzegorz" uniqKey="Opala G" first="Grzegorz" last="Opala">Grzegorz Opala</name><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Department of Neurology, Medical University of Silesia</s1><s2>Katowice</s2><s3>POL</s3><sZ>17 aut.</sZ><sZ>28 aut.</sZ></inist:fA14><country>Pologne</country></affiliation></author><author><name sortKey="Puschmann, Andreas" sort="Puschmann, Andreas" uniqKey="Puschmann A" first="Andreas" last="Puschmann">Andreas Puschmann</name></author><author><name sortKey="Quattrone, Aldo" sort="Quattrone, Aldo" uniqKey="Quattrone A" first="Aldo" last="Quattrone">Aldo Quattrone</name></author><author><name sortKey="Sharma, Manu" sort="Sharma, Manu" uniqKey="Sharma M" first="Manu" last="Sharma">Manu Sharma</name><affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases</s1><s2>Tübingen</s2><s3>DEU</s3><sZ>19 aut.</sZ><sZ>31 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></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="Stefanis, Leonidas" sort="Stefanis, Leonidas" uniqKey="Stefanis L" first="Leonidas" last="Stefanis">Leonidas Stefanis</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="Valente, Enza Maria" sort="Valente, Enza Maria" uniqKey="Valente E" first="Enza Maria" last="Valente">Enza Maria Valente</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Mendel Laboratory IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo</s1><s3>ITA</s3><sZ>13 aut.</sZ><sZ>35 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Vilarino Guell, Carles" sort="Vilarino Guell, Carles" uniqKey="Vilarino Guell C" first="Carles" last="Vilarino-Güell">Carles Vilarino-Güell</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, FL</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>36 aut.</sZ><sZ>41 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></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 K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name></author><author><name sortKey="Xiromerisiou, Georgia" sort="Xiromerisiou, Georgia" uniqKey="Xiromerisiou G" first="Georgia" last="Xiromerisiou">Georgia Xiromerisiou</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Department of Neurology, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></inist:fA14><country>Grèce</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Institute of Biomedical Research and Technology, CERETETH</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></inist:fA14><country>Grèce</country></affiliation></author><author><name sortKey="Maraganore, Demetrius M" sort="Maraganore, Demetrius M" uniqKey="Maraganore D" first="Demetrius M." last="Maraganore">Demetrius M. Maraganore</name></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="1"><inist:fA14 i1="03"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, FL</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>36 aut.</sZ><sZ>41 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author></analytic><series><title level="j" type="main">Annals of neurology</title><title level="j" type="abbreviated">Ann. neurol.</title><idno type="ISSN">0364-5134</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Annals of neurology</title><title level="j" type="abbreviated">Ann. neurol.</title><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Joint</term><term>Nervous system diseases</term><term>Parkinson disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Articulation</term></keywords></textClass></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 (rs1 052553, 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.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0364-5134</s0></fA01><fA02 i1="01"><s0>ANNED3</s0></fA02><fA03 i2="1"><s0>Ann. neurol.</s0></fA03><fA05><s2>69</s2></fA05><fA06><s2>5</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Independent and Joint Effects of the MAPT and SNCA Genes in Parkinson Disease</s1></fA08><fA11 i1="01" i2="1"><s1>ELBAZ (Alexis)</s1></fA11><fA11 i1="02" i2="1"><s1>ROSS (Owen A.)</s1></fA11><fA11 i1="03" i2="1"><s1>IOANNIDIS (John P. A.)</s1></fA11><fA11 i1="04" i2="1"><s1>SOTO-ORTOLAZA (Alexandra I.)</s1></fA11><fA11 i1="05" i2="1"><s1>MOISAN (Frederic)</s1></fA11><fA11 i1="06" i2="1"><s1>AASLY (Jan)</s1></fA11><fA11 i1="07" i2="1"><s1>ANNESI (Grazia)</s1></fA11><fA11 i1="08" i2="1"><s1>BOZI (Maria)</s1></fA11><fA11 i1="09" i2="1"><s1>BRIGHINA (Laura)</s1></fA11><fA11 i1="10" i2="1"><s1>CHARTIER-HARLIN (Marie-Christine)</s1></fA11><fA11 i1="11" i2="1"><s1>DESTEE (Alain)</s1></fA11><fA11 i1="12" i2="1"><s1>FERRARESE (Carlo)</s1></fA11><fA11 i1="13" i2="1"><s1>FERRARIS (Alessandro)</s1></fA11><fA11 i1="14" i2="1"><s1>GIBSON (J. Mark)</s1></fA11><fA11 i1="15" i2="1"><s1>GISPERT (Suzana)</s1></fA11><fA11 i1="16" i2="1"><s1>HADJIGEORGIOU (Georgios M.)</s1></fA11><fA11 i1="17" i2="1"><s1>JASINSKA-MYGA (Barbara)</s1></fA11><fA11 i1="18" i2="1"><s1>KLEIN (Christine)</s1></fA11><fA11 i1="19" i2="1"><s1>KRUGER (Rejko)</s1></fA11><fA11 i1="20" i2="1"><s1>LAMBERT (Jean-Charles)</s1></fA11><fA11 i1="21" i2="1"><s1>LOHMANN (Katja)</s1></fA11><fA11 i1="22" i2="1"><s1>VAN DE LOO (Simone)</s1></fA11><fA11 i1="23" i2="1"><s1>LORIOT (Marie-Anne)</s1></fA11><fA11 i1="24" i2="1"><s1>LYNCH (Timothy)</s1></fA11><fA11 i1="25" i2="1"><s1>MELLICK (George D.)</s1></fA11><fA11 i1="26" i2="1"><s1>MUTEZ (Eugenie)</s1></fA11><fA11 i1="27" i2="1"><s1>NILSSON (Christer)</s1></fA11><fA11 i1="28" i2="1"><s1>OPALA (Grzegorz)</s1></fA11><fA11 i1="29" i2="1"><s1>PUSCHMANN (Andreas)</s1></fA11><fA11 i1="30" i2="1"><s1>QUATTRONE (Aldo)</s1></fA11><fA11 i1="31" i2="1"><s1>SHARMA (Manu)</s1></fA11><fA11 i1="32" i2="1"><s1>SILBURN (Peter A.)</s1></fA11><fA11 i1="33" i2="1"><s1>STEFANIS (Leonidas)</s1></fA11><fA11 i1="34" i2="1"><s1>UITTI (Ryan J.)</s1></fA11><fA11 i1="35" i2="1"><s1>VALENTE (Enza Maria)</s1></fA11><fA11 i1="36" i2="1"><s1>VILARINO-GÜELL (Carles)</s1></fA11><fA11 i1="37" i2="1"><s1>WIRDEFELDT (Karin)</s1></fA11><fA11 i1="38" i2="1"><s1>WSZOLEK (Zbigniew K.)</s1></fA11><fA11 i1="39" i2="1"><s1>XIROMERISIOU (Georgia)</s1></fA11><fA11 i1="40" i2="1"><s1>MARAGANORE (Demetrius M.)</s1></fA11><fA11 i1="41" i2="1"><s1>FARRER (Matthew J.)</s1></fA11><fA14 i1="01"><s1>INSERM, U708, Neuroepidemiology</s1><s2>75013, Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="02"><s1>UPMC Univ Paris 06, UMR-S708, Neuroepidemiology</s1><s2>75005, Paris</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></fA14><fA14 i1="03"><s1>Division of Neurogenetics, Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, FL</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>36 aut.</sZ><sZ>41 aut.</sZ></fA14><fA14 i1="04"><s1>Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of loannina Medical School</s1><s2>loannina</s2><s3>GRC</s3><sZ>3 aut.</sZ></fA14><fA14 i1="05"><s1>Tufts Clinical and Translational Science Institute, Tufts Medical Center, and Tufts University School of Medicine</s1><s2>Boston, MA</s2><s3>USA</s3><sZ>3 aut.</sZ></fA14><fA14 i1="06"><s1>Department of Neurology, St Olav Hospital</s1><s2>Trondheim</s2><s3>NOR</s3><sZ>6 aut.</sZ></fA14><fA14 i1="07"><s1>Institute of Neurological Sciences, National Research Council</s1><s2>Cosenza</s2><s3>ITA</s3><sZ>7 aut.</sZ></fA14><fA14 i1="08"><s1>General Hospital of Syros, Syros, and Second Department of Neurology, University of Athens Medical School</s1><s2>Athens</s2><s3>GRC</s3><sZ>8 aut.</sZ></fA14><fA14 i1="09"><s1>Department of Neurology and Neuroscience, University of Milano-Bicocca, San Gerardo Hospital</s1><s2>Monza</s2><s3>ITA</s3><sZ>9 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="10"><s1>UMR 837 INSERM</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></fA14><fA14 i1="11"><s1>Univ Lille Nord de France</s1><s2>Lille</s2><s3>FRA</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>26 aut.</sZ></fA14><fA14 i1="12"><s1>University Hospital, CHRU</s1><s2>Lille</s2><s3>FRA</s3><sZ>11 aut.</sZ><sZ>26 aut.</sZ></fA14><fA14 i1="13"><s1>Mendel Laboratory IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo</s1><s3>ITA</s3><sZ>13 aut.</sZ><sZ>35 aut.</sZ></fA14><fA14 i1="14"><s1>Department of Neurology, Royal Victoria Hospital</s1><s2>Belfast</s2><s3>IRL</s3><sZ>14 aut.</sZ></fA14><fA14 i1="15"><s1>Department of Neurology, Goethe University</s1><s2>Frankfurt am Main</s2><s3>DEU</s3><sZ>15 aut.</sZ><sZ>22 aut.</sZ></fA14><fA14 i1="16"><s1>Department of Neurology, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></fA14><fA14 i1="17"><s1>Institute of Biomedical Research and Technology, CERETETH</s1><s2>Larissa</s2><s3>GRC</s3><sZ>16 aut.</sZ><sZ>39 aut.</sZ></fA14><fA14 i1="18"><s1>Department of Neurology, Medical University of Silesia</s1><s2>Katowice</s2><s3>POL</s3><sZ>17 aut.</sZ><sZ>28 aut.</sZ></fA14><fA14 i1="19"><s1>Section of Clinical and Molecular Neurogenetics at the Department of Neurology, University of Lübeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>18 aut.</sZ><sZ>21 aut.</sZ></fA14><fA14 i1="20"><s1>Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases</s1><s2>Tübingen</s2><s3>DEU</s3><sZ>19 aut.</sZ><sZ>31 aut.</sZ></fA14><fA17 i1="01" i2="1"><s1>Epidemiology of Parkinson's Disease (GEO-PD) consortium</s1><s3>INC</s3></fA17><fA20><s1>778-792</s1></fA20><fA21><s1>2011</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>16555</s2><s5>354000191534290030</s5></fA43><fA44><s0>0000</s0><s1>© 2011 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>47 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>11-0248600</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Annals of neurology</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>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 (rs1 052553, 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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B17</s0></fC02><fC02 i1="02" i2="X"><s0>002B17G</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Maladie de Parkinson</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Parkinson disease</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s2>NM</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Articulation</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Joint</s0><s5>09</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Articulación</s0><s5>09</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Système ostéoarticulaire</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Osteoarticular system</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Sistema osteoarticular</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>41</s5></fC07><fN21><s1>164</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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